C. O'Hear
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
G. Sellam
Employment or leadership position: F. HoffmannLa Roche Ltd
Stock ownership: F. HoffmannLa Roche Ltd
N. Horowitz
Employment or leadership position: Rambam Health Care Campus
Consultant or advisory role: F. HoffmannLa Roche Ltd
Honoraria: F. HoffmannLa Roche Ltd
Research funding: Takeda, Jonson
241 |ANTITUMORAL ACTIVITY OF THE NOVEL BTK
INHIBITOR TG1701 IS ASSOCIATED WITH DISRUPTION OF
IKAROS SIGNALING AND IMPROVEMENT OF ANTICD20
THERAPY IN BCELL NONHODGKIN LYMPHOMA
M. L. Ribeiro
1
, D. ReyesGarau
1
, M. Vinyoles
1
, N. ProfitosPeleja
1
, J.
C. Santos
1
, M. Armengol
1
, M. FernandezSerrano
1
, J. J. BechSerra
1
,
P. Blecua
1
, E. Musulen
1
, C. De la Torre
1
, H. Miskin
2
, M. Esteller
1
, F.
Bosch
3
, P. Menendez
1
, E. Normant
2
, G. Roue
1
1
Josep Carreras Leukaemia Research Institute, Lymphoma Translational
group, Badalona, Spain,
2
TG Therapeutics, Inc, Preclinical Sciences, New
York, New York, USA,
3
Vall d'Hebron Institute of Oncology, Experimental
Hematology, Barcelona, Spain
Introduction: Covalent Bruton's tyrosine kinase inhibitors (BTKis)
have transformed the treatment of Bcell nonHodgkin lymphoma (B
NHL). However, their activity has been often limited by 1) acquired
resistance due to the development of a cysteine to serine mutation at
the BTK catalytic site (BTKC481S) or overactivation of the NFkB
pathway, and 2) offtarget activity that precluded their use in com-
bination with antiCD20 antibodies. TG1701 is a novel irreversible
and highly specific BTKi currently under study in patients with
relapsed/refractory (R/R) BNHL alone and in combination with
ublituximab, a new glycoengineered antiCD20 antibody, and
umbralisib, a dual PI3Kδand casein kinase1εinhibitor (also referred
to as the U2 regimen).
Methods: A set of 6 BNHL clinical samples from TG1701 phase 1 trial
were characterized by phosphoproteomic and RNAseq analysis, fol-
lowed by biomarker validations using realtime PCR and western blot.
Activity of TG1701 either alone or in combination with U2 regimen
was evaluated by proliferation, antibodydependent cell cytotoxicity
(ADCC) and phagocytosis (ADCP) assays in a panel of n =10 BNHL co
cultures and in two mouse xenografts, including noncanonical NFκB
and BTKC481S resistant models. Biomarker validation and signal
transduction analysis were conducted through immunofluorescence,
immunohistochemical studies and gene knockout (KO) experiments.
Results: Phosphoproteomic analysis of tumoral lymphocytes from B
NHL patients receiving TG1701 led to a nonsupervised clustering
that matched the early clinical outcomes and separated a group of
early “responders” from a group of “nonresponders”. This clustering
was based on a selected list of 96 phosphosites, with IkarosSer442/
445 phosphorylation as a potential biomarker for TG1701 efficacy.
RNAseq analysis revealed that TG1701 treatment blunted the
Ikaros gene signature, including YES1, MYC and IRF4, in responder
patients as well as in BTKisensitive BNHL cell lines and xeno-
grafts. On the contrary, Ikaros nuclear activity and Ikaros
dependent gene regulation remained unaffected by the drug in
nonresponder patients and in BTKC481S , BTKKO and non
canonical NFκB models in vitro and in vivo. Interestingly, and in
contrast with the firstinclass BTKI, ibrutinib, TG1701 did not
impair FcγRdriven ADCC and ADCP triggered by the antiCD20
antibodies rituximab and ublituximab in different BNHL co
culture system, and cooperated with U2 in reducing the tumor
growth in both ibrutinibsensitive and ibrutinibinsensitive mouse
models of BNHL.
Conclusions: Altogether, these data validate phosphoproteomic as a
valuable tool for the early detection of response to BTK inhibition in
the clinic, and for the determination of drug mechanism of action.
Our results also support the use of TG1701U2 combination in R/R
BNHL patients, irrespective of prior response to ibrutinib.
EA previously submitted to regional or national meetings (up to
1000 attendees).
The research was funded by: TG Therapeutics, Fondo de Inves-
tigación Sanitaria PI18/01383, European Regional Development
Fund (ERDF) “Una manera de hacer Europa” (to GR).
Keywords: Molecular Targeted Therapies, Aggressive Bcell
nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
G. Roue
Employment or leadership position: H. Miskin and E. Normant are
employees with stock ownership in TG Therapeutics, Inc
Research funding: G.Roué received research funding from TG
Therapeutics
242 |PROMISING CLINICAL DATA FROM DOSE ESCALATION
IN A PHASE IB/II ONGOING STUDY OF MOSUNETUZUMAB WITH
POLATUZUMAB VEDOTIN FOR RELAPSED/REFRACTORY BCELL
NONHODGKIN'S LYMPHOMA
C. Diefenbach
1
, E. Budde
2
, J. Chavez
3
, I. S. Lossos
4
, A. Mehta
5
, K.
Dorritie
6
, M. Kamdar
7
, R. Negricea
8
, S. Pham
9
, M. Hristopoulos
10
,
LingY. Huw
11
, C. O’Hear
12
, Y. Oki
13
, I. To
14
, N. Ghosh
15
1
Perlmutter Cancer Center at NYU Langone Health, Division of
Hematology and Medical Oncology, New York, USA,
2
City of Hope
National Medical Center, Hematology & Hematopoietic Cell
Transplantation, Duarte, California, USA,
3
Moffitt Cancer Center,
Malignant Hematology, Tampa, USA,
4
Sylvester Comprehensive Cancer
Center, University of Miami Health System, Division of Hematology,
330
-
SUPPLEMENT ABSTRACTS
Miami, USA,
5
O’Neal Comprehensive Cancer Center at The University of
Alabama at Birmingham, Division of Hematology and Oncology,
Birmingham, USA,
6
UPMC Hillman Cancer Center, Division of
Hematology/Oncology, Pittsburgh, USA,
7
University of Colorado Cancer
Center, MedicineHematology, Aurora, Colorado, USA,
8
F. HoffmannLa
Roche Ltd, Product Development Clinical Safety, Basel, Switzerland,
9
F.
HoffmannLa Roche Ltd, Product Development Biometrics, Biostatistics,
Mississauga, Canada,
10
Genentech, Inc., In Vivo Pharmacology, South San
Francisco, USA,
11
Genentech, Inc., Department of Oncology Biomarker
Development, South San Francisco, USA,
12
Genentech, Inc., Product
Development Hematology, South San Francisco, USA,
13
Genentech, Inc.,
Product Development Oncology, South San Francisco, USA,
14
Genentech,
Inc., Product Development Clinical Science, South San Francisco, USA,
15
Levine Cancer Institute/Atrium Health, Hematologic Oncology and
Blood Disorders, Charlotte, USA
Introduction: Mosunetuzumab (M), a fulllength, humanized, IgG1
bispecific antibody targeting CD20 and CD3, has shown promising
efficacy and safety as monotherapy for relapsed/refractory (R/R) B
cell nonHodgkin's lymphoma (BNHL; NCT02500407; Assouline,
et al. ASH 2020). The combination of M with the antiCD79b
antibodydrug conjugate, polatuzumab vedotin (Pola), showed syn-
ergistic antilymphoma activity in a mouse xenograft model. These
data supported a Phase Ib/II, openlabel, multicenter trial of MPola
for R/R BNHL (GO40516, NCT03671018). Here we present early
clinical data from the Phase Ib cohort.
Methods: Patients (pts) with R/R follicular lymphoma (FL, grade [Gr]
1–3a) or aggressive NHL (aNHL), including de novo diffuse large Bcell
lymphoma (DLBCL), transformed FL (trFL) and FL Gr 3b (FL3b),
received Cycle (C) 1 stepup doses of M on Day (D) 1 (1mg) and D8
(2mg), the target dose on C1D15, then continued at the target dose
on C2D1 onwards. M was given every 21 days for eight cycles (or 17
cycles if stable disease or a partial response after C8). Pola (1.8mg/
kg) was given with M on D1 of each cycle for six cycles.
Results: As of November 17, 2020, 22 pts had received MPola (M
target doses: 9mg, n =7; 20mg, n =3; 40mg, n =6; 60mg [with D1
dose of 30mg from C3 onwards], n =6). Pts had DLBCL (n =12), FL
(n =3), FL3b (n =3) and trFL (n =4). Pt characteristics include:
median age of 70 (38–81) years; median of 3 (1–10) prior lines of
therapy; 7 (32%) pts had prior CART therapy; 17 (77%) and 19 (86%)
pts had disease refractory to last prior therapy and prior antiCD20
therapy, respectively. Median followup duration was 9.6 (0.7–23.7)
months. The most frequent treatmentrelated adverse events (AEs)
were neutropenia (45.4%), fatigue, nausea and diarrhea (all 36.4%).
Cytokine release syndrome (CRS) was observed in 2 pts (9.1%; both
Gr 1 by ASTCT 2019 criteria). One doselimiting toxicity (Gr 3 new
onset atrial fibrillation) was observed in the 40mg cohort. The
maximum tolerated dose was not exceeded. The most common Gr 3
and serious AEs were both neutropenia, observed in 8 (36.4%) and 3
(13.6%) pts, respectively. Two (9.3%) Gr 5 AEs occurred: sudden
cardiac death (n =1) and respiratory failure (n =1); neither was
deemed treatment related. No immune effector cellassociated
neurotoxicity was observed. The Table shows preliminary efficacy
data.
Conclusions: These data indicate that MPola has an acceptable
safety profile, with no Gr 2 CRS observed, and promising efficacy in
pts with R/R NHL with predominantly aggressive disease. The Phase
II expansion cohort in R/R DLBCL is ongoing, with no mandatory
hospitalization required.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: F. HoffmannLa Roche Ltd. Thirdparty
medical writing assistance, under the direction of the authors, was
provided by Katie Buxton and Khalida Rizi of Ashfield MedComms, an
Ashfield Health company, and was funded by F. HoffmannLa Roche
Ltd.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
C. Diefenbach
Consultant or advisory role: Seattle Genetics, Bayer, BristolMyers
Squibb, F. HoffmannLa Roche Ltd/Genentech, Inc., Merck, Janssen,
Celgene, MorphoSys
Stock ownership: Gilead Sciences
Research funding: Seattle Genetics, Genentech, Inc., Incyte, LAM
Therapeutics, Merck, BristolMyers Squibb, Millennium, F. Hoffmann
La Roche Ltd/Genentech, Inc., Janssen, MEI Pharma, Trillium
Therapeutics
E. Budde
Consultant or advisory role: F. HoffmannLa Roche Ltd/Genentech,
Inc., Kite/Gilead, Novartis
Honoraria: AstraZeneca
Research funding: Merck, Amgen, MustangBio, AstraZeneca
TABLE: Preliminary efficacy in the doseescalation cohort
SUPPLEMENT ABSTRACTS
-
331
Educational grants: F. HoffmannLa Roche Ltd/Genentech, Inc., Kite/
Gilead, AstraZeneca
Other remuneration: Speakers' bureau: Kite, AstraZeneca; Patents,
royalties, other intellectual property: patents pending
J. Chavez
Consultant or advisory role: Kite/Gilead, Bayer, Novartis, Kar-
yopharm Therapeutics, Verastem, Pfizer, MorphoSys, TeneoBio, Juno
Therapeutics, Celgene
Research funding: Merck
Other remuneration: Speakers' Bureau: Kite/Gilead, Genentech, Inc.,
AstraZeneca, BeiGene
I. S. Lossos
Consultant or advisory role: Seattle Genetics, Janssen Scientific Af-
fairs, Verastem
Honoraria: Janssen Biotech
Research funding: National Cancer Institute
Other remuneration: Royalties: Stanford
A. Mehta
Consultant or advisory role: Spectrum Pharmaceuticals, Aileron
Therapeutics, BristolMyers Squibb, Seattle Genetics, Kite, Pharma-
cyclics, TG Therapeutics, Incyte, Kyowa Kirin International, Rigel
Research funding: Incyte, F. HoffmannLa Roche Ltd/Genentech, Inc.,
Merck, BristolMyers Squibb, Juno Therapeutics, Gilead Sciences,
Forty Seven, Takeda, Astex Pharmaceuticals, Pharmacyclics/Janssen,
Epizyme, Aileron Therapeutics, Oncotartis, ADC Therapeutics, Seat-
tle Genetics, Innate Pharma, TG Therapeutics, Affirmed Therapeutics,
ADC Therapeutics, Rhizen Pharmaceuticals
Other remuneration: Speakers' bureau: Spectrum Pharmaceuticals,
Kite, Gilead Sciences, Seattle Genetics, Incyte
K. Dorritie
Honoraria: OncLive
Research funding: Kite, F. HoffmannLa Roche Ltd/Genentech, Inc.,
Juno Therapeutics, Nordic Nanovector, Genmab/Seattle Genetics,
Janssen Research & Development
Educational grants: Kite, Nordic Nanovector
M. Kamdar
Consultant or advisory role: AstraZeneca, Celgene, Pharmacyclics/
Janssen, Adaptive Biotechnologies, Karyopharm Therapeutics, Abb-
Vie, BeiGene
Research funding: TG Therapeutics
Other remuneration: Speakers' Bureau: Seattle Genetics
R. Negricea
Employment or leadership position: F. HoffmannLa Roche Ltd
S. Pham
Employment or leadership position: Roche Institute for Clinical
Evaluative Sciences
M. Hristopoulos
Employment or leadership position: Genentech, Inc.
Stock ownership: Genentech, Inc.
LingY. Huw
Employment or leadership position: Genentech, Inc.
Stock ownership: Genentech, Inc.
Educational grants: Genentech, Inc.
C. O’Hear
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
Y. Oki
Employment or leadership position: Genentech, Inc.; Immediate
family member: Jazz Pharmaceuticals
I. To
Employment or leadership position: Genentech, Inc.
Educational grants: Genentech, Inc.
N. Ghosh
Consultant or advisory role: Seattle Genetics, TG Therapeutics,
AstraZeneca, Verastem, Pharmacyclics/Janssen, Karyopharm Thera-
peutics, Genmab, BristolMyers Squibb, Gilead Sciences, Adaptive
Biotechnologies, BeiGene
Research funding: Pharmacyclics, TG Therapeutics, F. HoffmannLa
Roche Ltd/Genentech, Inc., Seattle Genetics, Juno Therapeutics,
Forty Seven
Other remuneration: Speakers' bureau: AbbVie, Janssen Oncology,
Kite/Gilead, Seattle Genetics, AstraZeneca, BristolMyers Squibb,
Celgene, Pharmacyclics/Janssen, Epizyme
243 |POLATUZUMAB VEDOTIN +RITUXIMAB +
LENALIDOMIDE IN PATIENTS (PTS) WITH RELAPSED/
REFRACTORY (R/R) DIFFUSE LARGE BCELL LYMPHOMA
(DLBCL): PRIMARY ANALYSIS OF A PHASE 1B/2 TRIAL
C. Diefenbach
1
, P. Abrisqueta
2
, E. GonzalezBarca
3
, C. Panizo
4
, J.
Maria Arguinano Perez
5
, F. Miall
6
, M. BastosOreiro
7
, A. Lopez
Guillermo
8
, L. Banerjee
9
, A. McMillan
10
, J. Hirata
11
, L. Musick
11
, S.
Saha
12
, B. Croft
11
, E. Seymour
13
1
Perlmutter Cancer Center at NYU Langone Health, New York, New York,
USA,
2
Hospital Vall Hebron, Department of Haematology, Barcelona,
Spain,
3
Instititut Catala D'Oncologia, IDIBELL, Universitat de Barcelona,
Barcelona, Spain,
4
Clínica Universidad de Navarra, IdiSNA, Servicio de
Hematología, Pamplona, Spain,
5
Complejo Hospitalario de Navarra,
Department of Haematology, Pamplona, Spain,
6
University Hospitals of
Leicester NHS Trust, Department of Haematology, Leicester, UK,
7
Hospital
General Universitario Gregorio Marañón, Department of Haematology,
Madrid, Spain,
8
Hospital Clínic de Barcelona, Department of
Haematology, Barcelona, Spain,
9
Maidstone and Tunbridge Wells NHS
Trust, Oncology Centre, Kent, UK,
10
Nottingham University Hospitals NHS
Trust, Centre for Clinical Haematology, Nottingham, UK,
11
Genentech,
Inc., Product Development Oncology, South San Francisco, USA,
12
F.
HoffmannLa Roche Ltd, Product Development Biometrics, Welwyn Gar-
den City, UK,
13
Karmanos Cancer Institute/Wayne State University,
Department of Oncology, Detroit, USA
332
-
SUPPLEMENT ABSTRACTS
Introduction: The combination of polatuzumab (Pola) +rituximab
(R) +lenalidomide (Len) may enhance antitumor response in R/R
DLBCL. Here, we report the primary analysis of the R/R DLBCL
cohort in a Phase 1b/2 study (GO29834; NCT02600897).
Methods: Pts received induction with 6 x 28Day (D) cycles (C) of:
Pola 1.8mg/kg intravenous (IV; C16: D1); R 375mg/m
2
IV (C16:
D1) and oral Len 10–20mg (dose escalation) or recommended Phase
2 dose (RP2D) daily on D1–21. Pts with a response at end of in-
duction (EOI) received 6 months (mo) consolidation with R 375mg/
m
2
(D1 every 2 mo) and Len 10mg (D1–21 monthly). Primary end-
points were safety/tolerability and positron emission tomography
(PET)complete response (CR) rate at EOI by independent review
committee (IRC) by modified Lugano criteria.
Results: At primary analysis (Sep 08, 2020), 57 pts were enrolled.
Median age was 71 years (range 28–92); male (67%); Ann Arbor
Stage III–IV (86%); International Prognostic Index 3–5 (60%); me-
dian 2 prior therapies; prior bone marrow transplant (11%); prior
CART therapy (5%); primary refractory (49%) and refractory to last
therapy (65%). Grade 3–4 adverse events (AEs) were experienced
by 75% of pts, most commonly, neutropenia (58%), thrombocyto-
penia (14%), infections (14%) and anemia (11%). AEs led to Len dose
reduction in 25% and interruption in 63% of pts. One Grade 5
treatmentrelated AE (neutropenic sepsis) was reported. In total, 49
pts were treated at RP2D (Pola 1.8mg/kg +Len 20mg). IRC PETCR
rate at EOI was 29% (Table). A best overall response (BOR)
assessed by investigator (INV) was seen in 36/49 (74%) pts with 17/
49 (35%) pts achieving a CR; of these, 14/17 (82%) remain in
remission at the cutoff date. Median duration of response (DOR)
was 8.1 mo (95% confidence interval [CI]: 4.7–not evaluable [NE]).
After a median followup of 9.7 mo, median progressionfree
survival (PFS) and overall survival (OS) were 6.3 mo (95% CI: 4.5–
9.7) and 10.9 mo (95% CI: 7.4–NE), respectively.
Conclusions: Our study of the novel triplet combination, PolaRLen,
demonstrates a tolerable safety profile. This first efficacy report of
PolaRLen shows promising activity in a difficulttotreat R/R
DLBCL population, particularly in pts achieving CR, a large propor-
tion of whom remain in remission at the cutoff date. Further eval-
uation of PolaRLen and the impact of consolidation therapy is
warranted to address the significant unmet need in this patient
population.
EA previously submitted to ASCO 2021.
The research was funded by: F. HoffmannLa Roche Ltd/Genentech,
Inc. Thirdparty editorial assistance, under the direction of the au-
thors, was provided by Angela Rogers, PhD, of Ashfield MedComms,
an Ashfield Health company, and was funded by F. HoffmannLa
Roche Ltd.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Molecular
Targeted Therapies Combination, Therapies
Conflicts of interests pertinent to the abstract
C. Diefenbach
Consultant or advisory role: Seattle Genetics, Bayer, BristolMyers
Squibb, Genentech, Inc./F. HoffmannLa Roche Ltd, Merck, Janssen,
Celgene, MorphoSys
Stock ownership: Gilead Sciences
Research funding: Seattle Genetics, Genentech, Inc., Incyte, LAM
Therapeutics, Merck, BristolMyers Squibb, Millennium, F. Hoffmann
La Roche Ltd/Genentech, Inc., Janssen, MEI Pharma, Trillium
Therapeutics
SUPPLEMENT ABSTRACTS
-
333
P. Abrisqueta
Consultant or advisory role: Janssen, F. HoffmannLa Roche Ltd,
Astrazeneca, Celgene, Abbvie
Honoraria: Janssen, F. HoffmannLa Roche Ltd, Astrazeneca, Cel-
gene, Abbvie, Gilead
E. GonzalezBarca
Consultant or advisory role: Janssen, AbbVie, Celgene, Gilead, Kiowa,
Eusapharma
Educational grants: Janssen, AbbVie, Takeda
Other remuneration: Speakers' bureau: Janssen, AbbVie, Takeda
C. Panizo
Consultant or advisory role: Roche Pharma
Educational grants: Roche Pharma
Other remuneration: Speakers' bureau: Janssen, Roche Pharma;
Expert testimony: Celgene, Incyte
J. Maria Arguinano Perez
Honoraria: Janssen, Takeda, F. HoffmannLa Roche Ltd, Celgene,
Novartis, Amgen
Educational grants: Amgen, Celgene, Janssen
Other remuneration: Speakers' bureau: Celgene, Janssen, Amgene
F. Miall
Consultant or advisory role: F. HoffmannLa Roche Ltd, Takeda
Honoraria: F. HoffmannLa Roche Ltd, Takeda
Educational grants: F. HoffmannLa Roche Ltd, Takeda
M. BastosOreiro
Consultant or advisory role: Kite, Celgene, F. HoffmannLa Roche Ltd
Research funding: F. HoffmannLa Roche Ltd
Educational grants: Kite, F. HoffmannLa Roche Ltd, Celgene, Takeda
Other remuneration: Speakers' bureau: F. HoffmannLa Roche Ltd,
Kite, Celgene, Takeda
A. LopezGuillermo
Consultant or advisory role: F. HoffmannLa Roche Ltd, Gilead/Kite,
Celgene, Incyte, Janssen
Research funding: F. HoffmannLa Roche Ltd, Gilead, Celgene
L. Banerjee
Educational grants: Gilead, Takeda, Novartis
A. McMillan
Consultant or advisory role: F. HoffmannLa Roche Ltd, AbbVie
Honoraria: F. HoffmannLa Roche Ltd, AbbVie
Educational grants: F. HoffmannLa Roche Ltd, Celgene/Bristol
Myers Squibb
Other remuneration: Speakers' bureau: F. HoffmannLa
Roche Ltd
J. Hirata
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
L. Musick
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd/GNE
S. Saha
Employment or leadership position: Genentech, Inc.
B. Croft
Employment or leadership position: Genentech, Inc.
Stock ownership: Genentech, Inc,/F. HoffmannLa Roche Ltd
E. Seymour
Employment or leadership position: Flatiron Health
Consultant or advisory role: Karyopharm, Janssen Oncology, Garner
Health
Stock ownership: F. HoffmannLa Roche Ltd
Research funding: Karyopharm
244 |SAFETY AND EFFICACY OF CD37TARGETING
NARATUXIMAB EMTANSINE PLUS RITUXIMAB IN DIFFUSE
LARGE BCELL LYMPHOMA AND OTHER NONHODGKIN'S B
CELL LYMPHOMAS A PHASE 2 STUDY
M. Y. Levy
1
, Z. GrudevaPopova
2
, M. Trneny
3
, W. Jurczak
4
, H. Pyly-
penko
5
, D. Jagadeesh
6
, M. Andre
7
, S. Nasta
8
, D. RechaviRobinson
9
, S.
Toffanin
9
, S. Micallef
9
, A. Attinger
9
, E. Rouits
9
, M. Dymkowska
9
, H.
Nauwelaerts
9
, F. J. S. H. WoeiAJin
10
1
Texas OncologyBaylor Charles A. Sammons Cancer Center, Dallas, TX,
USA, Department of Hematology, Medical Oncology, Dallas, USA,
2
Med-
ical University of Plovdiv, Department of Clinical Oncology, Plovdiv,
Bulgaria,
3
General Hospital, Charles University, Prague, Czech Republic,
4
Maria SklodowskaCurie National Research Institute of Oncology,
Department of Clinical Oncology, Krakow, Poland,
5
Cherkassy Regional
Oncological Center, Department of Hematology, Cherkassy, Ukraine,
6
Cleveland Clinic, Department of Hematologic Oncology and Blood Dis-
orders, Cleveland, USA,
7
UCL Namur, Centre Hospitalier Universitaire
Dinant Godinne, Yvoir, Belgium,
8
Perelman School of Medicine, University
of Pennsylvania, Division of Hematology/Oncology, Philadelphia, USA,
9
Debiopharm International S.A., Clinical Development, Lausanne,
Switzerland,
10
University Hospitals Leuven, Department of General
Medical Oncology, Leuven, Belgium
Introduction: Naratuximab emtansine (nara, Debio 1562, formerly
IMGN529) is an antibodydrug conjugate consisting of a humanized
antiCD37 antibody, K7153A, conjugated via a thioetherbased
linker to a cytotoxic maytansinoid, DM1. CD37, a lymphocyte sur-
face marker, is highly expressed in Bcell nonHodgkin lymphoma (B
NHL), including diffuse large Bcell lymphoma (DLBCL). In preclinical
models of BNHL, nara demonstrated strong antitumor activity,
further enhanced by coadministration of rituximab (RTX). A Phase 1
monotherapy study of nara revealed a good safety profile and
promising efficacy (22% overall response rate [ORR] in DLBCL at all
doses). Here we report results from an open label Phase 2 study to
334
-
SUPPLEMENT ABSTRACTS
evaluate the safety and efficacy of nara in combination with RTX in
patients (pts) with relapsed and/or refractory (R/R) DLBCL and other
forms of BNHL.
Methods: R/R BNHL pts with 16 prior lines of treatment were
recruited to two study parts. In Part 1, which included a safety runin,
pts received 0.7 mg/kg nara in combination with 375 mg/m
2
RTX
every 3 weeks (Q3W). In Part 2, only R/R DLBCL pts were included.
Pts were assigned to either the Q3W regimen, or to a weekly
regimen of 0.4, 0.2, and 0.2 mg/kg nara administered on days 1, 8, and
15, respectively, combined with 375 mg/m
2
RTX on day 1. Treatment
was administered for 6 cycles with possible extension. Primary
endpoints were treatment emergent adverse events (TEAEs) and
ORR. Safety is reported in all pts; efficacy only in DLBCL pts. Data
cutoff was 30Sep2020, when the trial was still ongoing; final data
from the end of study will be available in the full presentation (FP)
(NCT02564744).
Results: 100 pts were enrolled in the study: 80 DLBCL and 20 other
BNHL pts, of whom 82 (82%) experienced grade 3 TEAEs, the most
common being neutropenia 54 (54%), lymphopenia 17 (17%) and
thrombocytopenia 11 (11%). Only 10 (10%) pts discontinued nara
due to a TEAE. Only very few grade 3 TEAEs, known to be asso-
ciated with free DM1, were reported: 1 (1%) serious AE of toxic
hepatitis with no sequelae; and 2 (2%) cases of nonserious neurop-
athy (1 motor and 1 sensory). At the time of data cutoff, of the 80
DLBCL pts, 74 (32% refractory to 1
st
and/or last line) were efficacy
evaluable (had one screening assessment and at least one post
baseline tumor assessment or clinical progressive disease [PD]).
The ORR was 43.2%, with 24 (32.4%) complete responses and 8
(10.8%) partial responses. In addition, 11 (14.9%) stable disease and
31 (41.9%) PD were observed. Median duration of response was not
reached, (95% confidence interval 10.4 NA months [mo]). Median
duration of followup in responders was 13.7 mo.
Conclusions: The combination of nara with RTX was well tolerated,
with a manageable safety profile of expected, mainly hematological
AEs. A preliminary analysis shows promising efficacy. Final data,
regimen comparison, and related analyses will be available in the FP.
The research was funded by: Debiopharm International S.A.
Keywords: Molecular Targeted Therapies, Aggressive Bcell non
Hodgkin lymphoma, Combination Therapies
Conflicts of interests pertinent to the abstract
M. Trneny
Consultant or advisory role: Celgene, Janssen, Gilead, BristolMeyers
Squibb, Amgen, Abbvie, Takeda, F. HoffmannLa Roche Ltd, Mor-
phoSys, Incyte
Honoraria: Janssen, Gilead, BristolMeyers Squibb, Amgen, Abbvie,
Takeda, F. HoffmannLa Roche Ltd, MorphoSys, Incyte
Educational grants: Abbvie, Gilead, BristolMeyers Squibb, Takeda, F.
HoffmannLa Roche Ltd., Janssen
W. Jurczak
Consultant or advisory role: Mei pharma, Debiopharm, Loxo, Takeda,
Acerta, Astra Zeneca, Beigene
Research funding: GSK, Acerta, Astra Zeneca, Bayer, Beigene, Nordic
Nanovector, Incyte, Debiopharm, Genenthech, Janssen, Loxo, Mei
Pharma, Morphosys, Takeda, TG Therapeutics, Gilead
S. Nasta
Consultant or advisory role: Merck (DSMB)
Honoraria: Morphosys (Advisory Board)
Research funding: Debiopharm, ATARA, Roche, Rafael, Takeda/Mil-
lenium, Pharmacyclics
D. RechaviRobinson
Employment or leadership position: Employed by Debiopharm In-
ternational S.A.
S. Toffanin
Employment or leadership position: Employed by Debiopharm In-
ternational S.A.
S. Micallef
Employment or leadership position: Debiopharm International R&D;
Biostatistics & Data Management Biostatistics Program Lead
A. Attinger
Employment or leadership position: Debiopharm International S.A.
E. Rouits
Employment or leadership position: Debiopharm International S.A.
M. Dymkowska
Consultant or advisory role: Debiopharm International S.A., Argenx
BV, MorphoSys AG, Aurealis OY
H. Nauwelaerts
Employment or leadership position: Debiopharm International S.A.
245 |PROSPECTIVE EVALUATION OF LYMPHOMA RESPONSE
TO IMMUNOMODULATORY THERAPY CRITERIA (LYRIC) IN
GATA TRIAL FROM THE LYSA GROUP
Y. Al Tabaa
1
, O. Casasnovas
2
, C. Baillet
3
, E. Bachy
4
, E. Nicolas
Virelizier
5
, J. M. Schiano de Colella
6
, C. Bailly
7
, S. Kanoun
8
,
S. Guidez
9
, E. Gyan
10
, R. Gressin
11
, N. Morineau
12
, L. Ysebaert
13
,
S. Le Gouill
14
, H. Tilly
15
, R. Houot
16
, F. Morschhauser
17
,
G. Cartron
18
, C. Herbaux
18
1
Scintidoc, Nuclear Medicine Center, Montpellier, France,
2
CHU
François Mitterrand, Hematology, Dijon, France,
3
CHU Lille, Nuclear
Medicine, Lille, France,
4
CHU Lyon, Hematology, Lyon, France,
5
CRLC
Lyon, Hematology, Lyon, France,
6
Institut PaoliCalmettes, Hematology,
Marseille, France,
7
CHU Nantes, Nuclear Medicine, Nantes, France,
8
Oncopole Toulouse, Nuclear Medicine, Toulouse, France,
9
CHU Poit-
iers, Hematology, Poitiers, France,
10
CHU Tours, Hematology,
Tours, France,
11
CHU Grenoble, Hematology, Grenoble, France,
12
CHD
Vendée, Hematology, La Roche sur Yon, France,
13
Oncopole Tou-
louse, Hematology, Toulouse, France,
14
CHU Nantes, Hematology,
SUPPLEMENT ABSTRACTS
-
335
Nantes, France,
15
Centre Henri Becquerel, Hematology, Rouen,
France,
16
CHU Rennes, Hematology, Rennes, France,
17
CHU Lille,
Hematology, Lille, France,
18
CHU Montpellier, Hematology, Montpellier,
France
Introduction: Checkpoint blockade may complicate response
assessment by a flare reaction or pseudoprogression (PP). To avoid
the mistake of considering a new agent ineffective, it was pro-
posed to add the category “indeterminate response” (IR) to Lugano
classification, in the LYmphoma Response to Immunomodulatory
Therapy Criteria (LYRIC): 1/ increase in overall tumor burden in
the first 12 weeks of therapy, without clinical deterioration
(IR1), 2/ development of new lesions without overall progression
(IR2), or 3/ increased FDG avidity despite no change in lesion
size (IR3). These patterns are defined as progressive metabolic
disease (PMD) in the Lugano criteria. A PP was defined as an IR
that became a partial or complete metabolic response (PMR or
CMR) at next evaluation. The aim of this study is to assess in a
practical and prospective manner the LYRIC criteria in relapsed/
refractory (R/R) DLBCL and FL treated with atezolizumab, ven-
etoclax and obinutuzumab (GATA trial), and measuring the inci-
dence of PP.
Methods: The GATA study is a LYSA sponsored multicenter
phase 2 trial (NCT03276468) evaluating the combination of
atezolizumab, obinutuzumab and venetoclax in biopsyconfirmed
R/R DLBCL and FL patients who failed at least one line of ther-
apy (rituximab and anthracycline containing regimen). Local im-
aging practitioners used the Lugano and LYRIC classification.
Clinical investigators were warned of the possibility of PP, and
a coordinating investigator's approval was required before
stopping treatment. A centralized imaging review on PETCT scan
was performed at three time points: baseline, cycle 4 (C4, 12
weeks) and cycle 8 (C8, 24 weeks), on Lugano and LYRIC
criteria.
Results: Our study has included 116 patients (58 DLBCL, 58 FL)
from GATA trial. The overall metabolic response rate at C8 was
23.6% and 53.6% with a median follow up of 9 months and 14.5
months for DLBCL and FL patients, respectively. Ninetyfive pa-
tients had a centralized review at C4 and 57 at C8. Missing pa-
tients are those who progressed prior to the restaging by PETCT
scan. In Lugano criteria, 84 reviewed responses (88.4%) were
concordant with local response at C4, and 47 (82.5%) at C8. In
LYRIC criteria, 9 patients (4 DLBCL and 5 FL) were classified at C4
as IR by both local reading and centralized review, with a
discordance in the type of IR (1, 2 or 3) in 6/9 cases. During the
followup, 4 cases turned out to be PP (1 DLBCL and 3 FL) and 5
cases real progressive diseases (PD). One PP is illustrated in Figure
1 (IR3 at C4, CMR at C8). At C8, 7 patients were classified as IR
by centralized review (IR2 and IR3), only 2 of them were IR by
local reading. During the followup, all of those cases turned out to
be real PD within 1 to 3 cycles of therapy.
Conclusions: We observed a low frequency of 3.4% of PP at C4.
Interestingly, all IRs at C8 were found to be real PD. Overall, these
data are in favor of using the LYRIC classification, but only for early
evaluation.
EA previously submitted to EHA 2021.
Keywords: PETCT, Aggressive Bcell nonHodgkin lymphoma,
Indolent nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
ONGOING TRIALS
246 |RADIATION FREE THERAPY OR THE INITIAL
TREATMENT OF GOOD PROGNOSIS EARLY NONBULKY
HODGKIN LYMPHOMA, DEFINED BY A LOW METABOLIC
TUMOR VOLUME AND A NEGATIVE PET2RAFTING TRIAL
A. Gallamini
1
, J. Walewski
2
, A. Rambaldi
3
, S. Viviani
4
, A. Sureda
5
, M.
André
6
, C. Rossi
7
, A. Moccia
8
, E. Zucca
8
, D. Rossi
8
, A. Filippi
9
, M.
Meignan
10
, S. Chauvie
11
, J. M. Zaucha
12
1
Antoine Lacassagne Cancer Center, Research and Clinical Innovation, Nice,
France,
2
Marii SkłodowskiejCurie Institute, OncoHematology, Warsaw,
Poland,
3
Ospedale Papa Giovanni XXIII, Hematology, Bergamo, Italy,
4
Istituto Europeo di Ematologia, Hematology, Milano, Italy,
5
Institut Català
d'Oncologia, Hematology, Barcelona, Spain,
6
Cliniques universitaires Saint
Luc UC Louvain, Hematology, Louvain, Belgium,
7
CHU Bocage, Hematol-
ogy, Dijon, France,
8
Istituto Oncologico della Svizzera Italiana, Hematology,
Bellinzona, Switzerland,
9
Policlinico S. Matteo, IRCCS, Radiation Oncology,
Pavia, Italy,
10
Henry Mondor Hospital, LYSA Imaging, Paris, France,
11
Ospedale S. Croce e Carle, Medical Physics, Cuneo, Italy,
12
Medical Uni-
versity of Gdansk, Hematology, Gdansk, Poland
Introduction: Earlystage Hodgkin Lymphoma (eHL) is a curable
disease with a 5Y PFS and OS >8595% and 95%, respectively, after
combined modality treatment (CMT) with 24 cycles of chemo-
therapy (CT) followed by 20 or 30 Gy Involvednode radiotherapy
(RT). However, the efficacy of CMT is offset by a longterm morbidity,
with a cumulative incidence of Second Primary Malignancy (SPM) at
336
-
SUPPLEMENT ABSTRACTS
40 years of 48.5%, and a standardized incidence ratio 4.6 folds higher
than the agematched control population, with SPMs arising mostly
in areas included in RT fields (Schaapveld 2015). The RAFTING trial is
aimed to answer a still unmet need: is possible to deliver a RTfree
treatment in most patients (p.) with goodprognosis (no bulky, B
symptoms or extranodal) eHL (gpeHL), with a similar efficacy to
CMT? The RAFTING trial is expected to answer these questions: (1)
Main endpoint: could the majority of goodprognosis early cHL (gpe
cHL) be treated with 4 ABVD cycles with a 3Y PFS 90% with a
riskand responseadapted strategy? Secondary endpoints: (2) Could
we deliver RT “on demand” in gpecHL in “limited” relapse after CT
followed by Nivolumab maintenance (Nivom), with an acceptable
overall effectiveness? (3) Could we increase the effectiveness of CMT
in PET2 positive eHL by adding oneyear Nivom? (4) Could we
anticipate the diagnosis of an impending relapse during followup of
p. in CR after chemo alone by cellfree DNA monitoring?
Methods: In the RAFTING trial, a phase 2, multicenter, prospective
study sponsored by the Gdansk (PL) University, 160 nonbulky stage
IIIA HL p. will be enrolled in 5 European countries with an accrual
time of 18 months and a minimum followup of 36 months. For
treatment planning p. will be stratified into three risk categories
according to (a) modified EORTC criteria (mEORTC), (b) interim PET
after 2 ABVD (PET2) and (3) Metabolic Tumor Volume (MTV)
computed in baseline PET. In the mEORTC criteria bulky and B
symptoms were taken over by a “Large Nodal Mass”, with the
largest diameter 5 cm., which proved a poor response predictor in
stage IIIA, PET2 negative HL p. treated with chemo alone (IIlidge
2020). P. stratification: (1): P. with a negative PET2 and a low MTV
(P. group 1: 80%), will be treated with 2 or 4 ABVD cycles according
to their mEORTC risk and upon CR entry, they will be addressed to a
stringent clinical followup every 3 months, and cfDNA assay every 6
months for the first 18 months. (2) Low MTV and negative PET2 p.
failing firstline treatment with CT alone (P. group 2: 10%). As a
“limited relapse” (stage I II) is expected to occur in 6070% of cases
(André 2017, Bröckelman 2021), these p. will be treated with INRT
“on demand” at the dose of 36 Gy, followed by Nivom. (3): P. with a
positive PET2, whatever their MTV, or p. with a negative PET2 and
a high MTV (P. group 3: 10%). will be treated with 2 more ABVD
followed by INRT, 20 or 30 Gy, depending on the risk class according
to mEORTC criteria, and Nivom.
The research was funded by: he research was funded by the Polish
Medical Research Agency
Keywords: Ongoing Trials
No conflicts of interests pertinent to the abstract.
247 |ANIMATE: A PHASE II STUDY OF NIVOLUMAB IN
TRANSPLANT ELIGIBLE PATIENTS WITH RELAPSED/
REFRACTORY CLASSIC HODGKIN LYMPHOMA
S. Booth
1
, A. Kirkwood
2
, P. Johnson
3
, S. Barrington
4
, E. Gallop
Evans
5
, K. Peggs
6
, V. Warbey
4
, C. Burton
7
, A. Ardavan
8
, B. Phillips
9
, E.
Lawrie
10
, L. Pike
4
, M. Northend
10
, L. CliftonHadley
10
, R. Jenner
10
, G.
P. Collins
1
SUPPLEMENT ABSTRACTS
-
337
1
Oxford University Hospitals, Department of Haematology, Oxford, UK,
2
UCL Cancer Institute, CR UK and UCL Cancer Trials Centre, London, UK,
3
University of Southampton, Department of Medicine, London, UK,
4
King's
College London, King's College London and Guys’ & St Thomas PET
Imaging Centre, London, UK,
5
Velindre University NHS Trust, Department
of Oncology, Cardiff, UK,
6
University College London Hospitals,
Haematology, London, UK,
7
Leeds Cancer Centre, Haematology, Leeds,
UK,
8
University of Oxford, Department of Physics, Oxford, UK,
9
University
of Manchester and Manchester Academic Health Science Centre, Division
of Cancer Science, Manchester, UK,
10
UCL Cancer Institute, CR UK and
UCL Cancer Trials Centre, London, UK
Background: Relapsed or refractory (R/R) classic Hodgkin lymphoma
(cHL) has a poor outlook with chemotherapy alone (longterm sur-
vival 1020%). In fit patients, non crossreacting salvage regimens
and high dose chemotherapy with autologous stem cell transplant
(ASCT) improve 5 year freedom from second failure (FF2F) to 42%.
Progressive disease, toxicity of salvage therapy and failure to harvest
stem cells are common barriers to ASCT. The most discriminating
reported prognostic factor for ASCT outcome is pretransplant
response by PET (35 year PFS >70% if PET negative; 2530% if
PET positive).
Programmed cell death protein 1 (PD1) inhibitors have estab-
lished efficacy in R/R cHL, with overall response rates (ORR) of 69
72% and complete metabolic response rates (CMR) of 1637%. PD1
inhibitors warrant exploration as salvage therapy because ORR ap-
pears to be at least as good as with cytotoxic chemotherapy or
brentuximab vedotin, they are not typically myelosuppressive, help-
ing preserve fitness, and responses are relatively durable allowing
time for transplant.
PD1 expression by immunohistochemistry (IHC) and 9p24 copy
gain by FISH are reported to correlate with response to PD1 in-
hibitors. Serial serum TARC (thymus and activationregulated che-
mokine) is reported to be prognostic in the frontline treatment of
cHL and may aid response assessment.
Methods: ANIMATE is a Phase II singlearm multicentre study in the
UK assessing the safety and efficacy of 48 doses of nivolumab 240
mg every 14 days as second or third line therapy for R/R cHL in
ASCTfit patients. Eligible patients must be 16 years, and about to
receive or be receiving first or second line therapy 14 days after
FIGURE 1 ANIMATE trial schema. PET CT Positorn emission tomography with contrast enhanced computed tomography *indeterminate
Response modified form Lymphoma Response to immunomodulatory Therapy Criteria of Cheson et al., 2016
338
-
SUPPLEMENT ABSTRACTS
last treatment in cycle 2 (cycle 3 or 4 if receiving brentuximab
vedotin)). Patients with autoimmune disorders, colitis, inflammatory
bowel disorders or pneumonitis are excluded. Trial treatment eligi-
bility, assessments and patient progress are shown in Fig 1.
The primary endpoint is ORR by PET after 48 cycles of nivolu-
mab. The study is powered to exclude an ORR <40% for which we
require 30 nivolumabtreated patients (A’Hern single arm design,
80% power and a onesided 0.1 alpha). We expect to register 75120
patients during salvage treatment. Secondary endpoints are: safety
and tolerability of nivolumab (including safety of subsequent alloge-
neic transplant); progression free survival and overall survival at one
year. Exploratory endpoints include: correlating disease response
with baseline PD1 copy number, PD1 expression by IHC, immune
profiling of tumour and peripheral blood by flow and gene expression
profiling; and assessment of whether response assessment can be
improved by combining PET with serum biomarkers e.g. TARC.
Since December 2018, 38 patients have been registered, of
whom 16 have been PET positive at the end of their current salvage
therapy and eligible for nivolumab.
Clinical trials.gov No. NCT03337919
The research was funded by: Bristol Myers Squibb
Keywords: Ongoing Trials
Conflicts of interests pertinent to the abstract
S. Barrington
Honoraria: Roche, Takeda
Educational grants: Takeda
C. Burton
Consultant or advisory role: Celgene, Bristol Myers Squibb
Foundation
Honoraria: Roche, Takeda
G. P. Collins
Consultant or advisory role: Roche, Takeda, Incyte, Pfizer, MSD,
Celgene, Beigene, Daiichi Sankyo, Celleron therpeutics, ADC
therapeutics
Honoraria: Roche, Takeda, Gilead Sciences, Pfizer, Novartis, Daiichi
Sankyo, Incyte, Celleron Therapeutics, MSD Oncology, BeiGene, ADC
Therapeutics
Research funding: MSD Oncology, Celegene, Celleron Therpeutics,
Bristol Myers Squibb, Amgen
Educational grants: Roche, Takeda
248 |BRENTUXIMAB VEDOTIN IN COMBINATION WITH
NIVOLUMAB, DOXORUBICIN, AND DACARBAZINE IN NEWLY
DIAGNOSED PATIENTS WITH ADVANCED HODGKIN
LYMPHOMA (SGN35027, TRIAL IN PROGRESS)
I. Flinn
1
, J. D. Friedman
2
, L. Ho
3
, H. J. Lee
4
1
Sarah Cannon Research Institute and Tennessee Oncology, Medical
Oncology, Nashville, Tennessee, USA,
2
University Hospitals, Seidman
Cancer Center, Cleveland, Ohio, USA,
3
Seagen Inc., Clinical Development,
Bothell, Washington, USA,
4
MD Anderson Cancer Center, Department of
Lymphoma & Myeloma, Houston, Texas, USA
Introduction: Brentuximab vedotin (BV) is approved for the treat-
ment of adults with treatmentnaïve Stage III or IV classical Hodgkin
lymphoma (cHL) in combination with doxorubicin, vinblastine, and
dacarbazine (AVD) (Connors 2017). Nivolumab is approved for
treatment of adults with relapsed/refractory cHL. Both agents have
been well tolerated with promising activity when combined with
multiagent chemotherapy. The combination of BV plus nivolumab
was evaluated as a frontline treatment option for patients (pts) with
cHL who are over 60 years and ineligible for or declined conventional
combination chemotherapy (Yasenchak 2020). The ongoing study
reported an overall response rate (ORR) of 82% in 11 pts and ap-
pears well tolerated in this population. In another trial in 93 pts in the
first salvage setting, the combination produced a 67% complete
response (CR) rate (Herrera 2018, Moskowitz 2019) and the majority
of pts were able to undergo subsequent stem cell transplant. It is
reasonable to expect that the combination of BV, nivolumab, A, and D
(AN+AD) will result in high response rates and be well tolerated, with
potentially less toxicity relative to A+AVD.
Methods: SGN35027 (EudraCT 202000402717) is an openlabel,
multiple part, multicenter, phase 2 clinical trial. Part A will evaluate
the efficacy and safety of A+AVD when administered with growth
factor prophylaxis in pts with Stage III/IV cHL. Part B will evaluate
the combination of AN+AD in pts with Stage I or II cHL with bulky
mediastinal disease or Stage III or IV cHL. Part C will evaluate the
efficacy and tolerability of AN+AD in pts with Stage I or II cHL
without bulky disease. The primary objective of Parts B and C is to
estimate the CR rate at end of treatment (EOT) in pts with treat-
mentnaïve cHL.
Approximately 240 pts will be enrolled in this study: approxi-
mately 40 in Part A, 50 in Part B, and 150 in Part C. Part A has
completed enrollment, and Part B is fully enrolled. Pts in Parts B and C
will be treated with BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25
mg/m
2
, and dacarbazine 375 mg/m
2
, administered separately by IV
infusion on Days 1 and 15 of each 28day cycle. Pts in Part B will receive
up to 6 cycles of treatment; pts in Part C will receive 4 cycles. Efficacy
will be assessed by PET/CT scans at Cycle 2 and EOT; disease response
and progression for Parts B and C will be assessed using the LYRIC
modification of the Lugano Classification Revised Staging System for
nodal nonHodgkin and Hodgkin lymphomas (Cheson 2016). Pts will be
followed for disease progression and overall survival for 5 years.
Enrollment is ongoing in the US, with plans for restofworld
expansion for Part C.
EA previously submitted to ASCO 2021.
The research was funded by: Seagen Inc.
Keywords: Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
I. Flinn
SUPPLEMENT ABSTRACTS
-
339
Consultant or advisory role: Abbvie; AstraZeneca; BeiGene;
Gilead Sciences; Janssen; Juno Therapeutics; Kite Pharma; Mor-
phoSys; Nurix; Roche; Seagen Inc.; Shanghai Yingli Pharmaceuticals;
Takeda; TG Therapeutics; Unum Therapeutics; Verastem
Stock ownership: Johnson & Johnson
Research funding: Abbvie; Acerta Pharma; Agios; ArQule;
AstraZeneca; BeiGene; Calithera Biosciences; Celgene; Constellation
Pharmaceuticals; Curis; FORMA Therapeutics; Forty Seven; Gen-
entech; Gilead Sciences; Incyte; Infinity Pharmaceuticals; Janssen;
Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Merck;
MorphoSys; Novartis; Pfizer; Pharmacyclics; Portola Pharmaceuti-
cals; Roche; Roche; Seagen Inc.; Takeda; Teva; TG Therapeutics;
Trillium Therapeutics; Unum Therapeutics; Verastem
J. D. Friedman
Consultant or advisory role: Celgene
Stock ownership: Abbott
Honoraria: Amgen; Celgene
Research funding: Seagen Inc./Astellas
L. Ho
Employment or leadership position: Seagen Inc.
Stock ownership: Seagen Inc.
Research funding: Seagen Inc.
Educational grants: Seagen Inc.
H. J. Lee
Consultant or advisory role: BristolMyers Squibb; Guidepoint Global
Research funding: BristolMyers Squibb; Celgene; Celgene; Oncter-
nal Therapeutics; Seagen Inc.; Takeda
249 |THE CLLRT1 TRIAL: A MULTICENTER PHASE2 TRIAL OF
ZANUBRUTINIB, A BTK INHIBITOR, PLUS TISLELIZUMAB, A PD1
INHIBITOR, FOR PATIENTS WITH RICHTER TRANSFORMATION
O. AlSawaf
1
, S. Robrecht
1
, J. Stumpf
1
, A.M. Fink
1
, M. Ritgen
2
, P.
Johansson
3
, E. Tausch
4
, M. Hoechstetter
5
, P. Staber
6
, U. Jäger
6
, C. U.
Niemann
7
, C. Pallasch
1
, K.A. Kreuzer
1
, S. Stilgenbauer
4
, K. Fischer
1
,
C. Wendtner
5
, M. Hallek
1
, B. Eichhorst
1
1
University Hospital of Cologne, Department I of Internal Medicine,
Cologne, Germany,
2
University of SchleswigHolstein, Department II of
Internal Medicine, Kiel, Germany,
3
University Hospital Essen, Clinic for
Hematology, Essen, Germany,
4
University Hospital Ulm, Department III of
Internal Medicine, Ulm, Germany,
5
Klinikum Schwabing, Department of
Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases
and Tropical Medicine, Munich, Germany,
6
Medical University of Vienna,
Department of Medicine I, Division of Hematology & Hemostaseology,
Vienna, Austria,
7
Department of Haematology, Rigshospitalet and
Department of Clinical Medicine, University of Copenhagen, Denmark,
Copenhagen, Denmark
Introduction: Richter Transformation (RT) is defined as trans-
formation of chronic lymphocytic leukemia (CLL) to diffuse large B
cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL). Overall prog-
nosis of patients with RT remains poor, with a median overall survival
of 6 8 months after diagnosis. Given the high average age of patients
with CLL, many patients might not be eligible for intensive chemo-
immunotherapy at the time of RT and are therefore in need of
effective and tolerable treatment options. In light of early data sug-
gesting efficacy of PD1 inhibitors and BTK inhibitors for patients with
RT, we designed an investigatorinitiated phase 2 study to test effi-
cacy and safety of tislelizumab, a PD1 inhibitor, with zanubrutinib, a
BTK inhibitor for patients with CLL and RT.
Methods: Key inclusion criteria are diagnosis of CLL according to
iwCLL, histopathological diagnosis of RT (DLBCL or HL) and previ-
ously untreated RT, RT with objective response to firstline RT
treatment or nontolerance to prior line of RT treatment. Key
exclusion criteria are primary progressive disease, more than one
prior line of RT therapy and allogeneic stem cell transplantation up to
100 days prior to screening.
Each treatment cycle 21 days) consists of one infusion of 200
mg tislelizumab at day 1 and 160 mg zanubrutinib twice daily orally.
Six cycles of induction are followed by 6 cycles of consolidation;
patients with complete response (CR), partial response (PR) or stable
disease (SD) continue maintenance until disease progression or non
tolerance. Patients with response to treatment can undergo alloge-
neic transplantation any time after induction therapy.
The primary endpoint is overall response rate (ORR) after in-
duction therapy according to the refined Lugano Classification. Sec-
ondary endpoints include response according to iwCLL, progression
free survival and overall survival.
Efficacy of the study treatment is assessed to be not effective if
the ORR is less than 40 % with corresponding null hypothesis H0:
ORR 0.40 and alternative hypothesis H1: ORR >0.40. It is assumed
to improve the ORR to at least 60 %. 48 eligible patients have to be
enrolled to achieve statistical significance with a power of 80%.
The trial was initiated in January 2020 and aims to complete
recruitment within 2.5 years. So far, 18 patients have been enrolled.
10 centers in Germany, 1 site in Austria and 1 site Denmark are open
for enrolment. Potential patients can be discussed any time at CLL
Studie@ukkoeln.de and +4922147888220.
The research was funded by: BeiGene
Keywords: OngoingTrials
Conflicts of interests pertinent to the abstract
O. AlSawaf
Research funding: Beigene
A.M. Fink
Honoraria: Celgene, Janssen, HoffmannLaRoche
M. Ritgen
Honoraria: HoffmannLaRoche, AbbVie
Research funding: HoffmannLaRoche,
U. Jäger
Honoraria: Novartis, Gilead, Celgene, Miltenyi, Janssen
340
-
SUPPLEMENT ABSTRACTS
Research funding: Novartis, Gilead, Celgene, Miltenyi, Janssen
C. U. Niemann
Research funding: Abbvie, Gilead, Janssen, Roche, CSL Behring,
Genmab, Sunesis, Astra Zeneca, Novo Nordisk Foundation
(NNF16OC0019302), Danish Ministry of Higher Education and
Science
K.A. Kreuzer
Honoraria: HoffmannLaRoche, AbbVie
Research funding: HoffmannLaRoche, AbbVie
S. Stilgenbauer
Honoraria: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La
Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem
Research funding: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoff-
mann LaRoche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem
K. Fischer
Honoraria: AbbVie, HoffmannLaRoche
C. Wendtner
Honoraria: HoffmannLaRoche, AbbVie, JanssenCilag, Gilead,
MorphoSys
M. Hallek
Honoraria: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharma-
cyclics, AbbVie
Research funding: Roche, Gilead, Mundipharma, Janssen, Celgene,
Pharmacyclics, AbbVie
B. Eichhorst
Honoraria: HoffmannLaRoche, Abbvie, Celgene, Novartis, ArQuele,
BeiGene, Gilead, AstraZeneca, Oxford Biomedica (UK), Adaptive
Biotechnologies
Research funding: HoffmannLaRoche, AbbVie, Janssen
250 |PHASE 3 TRIAL (GCT301305) OF EPCORITAMAB VERSUS
STANDARD OF CARE IN PATIENTS WITH RELAPSED OR
REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA (DLBCL)
C. Thieblemont
1
, M. R. Clausen
2
, A. S. Balari
3
, P. L. Zinzani
4
, C. P.
Fox
5
, S. Y. Kim
6
, S. D. Vindelov
7
, P. Lugtenburg
8
1
Assistance Publique & Hôpitaux de Paris (APHP), Hopital SaintLouis,
Université de Paris, HematoOncology Department, Paris, France,
2
Vejle
Hospital, Department of Hematology, Vejle, Denmark,
3
Institut Català
d'OncologiaHospital Duran i Reynals IDIBELL, Universitat de Barcelona,
Hospitalet del Llobregat, Department of Hematology, Barcelona, Spain,
4
Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of
Hematology “L. e A. Seràgnoli,” University of Bologna, Department of
Experimental, Diagnostic and Specialty Medicine, Bologna, Italy,
5
Not-
tingham University Hospitals NHS Trust UK, Department of Clinical
Haematology, Nottingham, UK,
6
AbbVie, Clinical Development, North
Chicago, Illinois, USA,
7
Genmab, Clinical Development, Copenhagen,
Denmark,
8
On behalf of the HOVON/Lymphoma Working Group, Erasmus
MC Cancer Institute, Department of Hematology, Rotterdam, Netherlands
Background: Patients (pts) with DLBCL who are refractory to/or
have relapsed (R/R) after treatment with chemotherapy and anti
CD20 monoclonal antibody (mAb) have poor prognosis. New treat-
ment options are needed to improve outcomes. Epcoritamab, a novel
subcutaneous (SC) bispecific antibody, binds to CD3 on T
lymphocytes and CD20 on Bcell nonHodgkin lymphoma (NHL)
cells. In an ongoing phase 1/2 doseescalation trial in heavily pre-
treated pts with Bcell NHL (N =68), epcoritamab showed a tolerable
safety profile and substantial singleagent antitumor activity, with a
complete response (CR) rate of 55% and an overall response rate of
91% in pts with R/R DLBCL (at 48 mg doses; n =12)
(NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable
R/R DLBCL pts previously treated with chimeric antigen receptor T
cell (CART) therapy achieved an objective response with 2 achieving
CR. These encouraging data support the potential for epcoritamab to
improve clinical outcomes in pts with R/R DLBCL. Here, we describe
the ongoing phase 3 trial of epcoritamab versus standard of care
(SOC) treatments in pts with R/R DLBCL.
Methods: GCT301305 is a global, randomized, openlabel, multi-
center, phase 3 study designed to evaluate the efficacy of epcor-
itamab versus investigator's choice of SOC with RGemOx
(rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab)
in adults with R/R disease of one the following CD20+Bcell NHL
histologies: I) DLBCL, not otherwise specified, including de novo
DLBCL or DLBCL histologically transformed from follicular lym-
phoma; II) “double or triplehit” DLBCL (highgrade Bcell lymphoma,
with MYC and BCL2 and/or BCL6 translocations), including de novo
SUPPLEMENT ABSTRACTS
-
341
“doublehit” or “triplehit” DLBCL or “doublehit” or “triplehit”
DLBCL histologically transformed from follicular lymphoma; or III)
follicular lymphoma grade 3B. Other key eligibility criteria include:
1 line of prior chemotherapy that included treatment with an anti
CD20 mAb, Eastern Cooperative Oncology Group performance sta-
tus 0–2, and prior failure of/ineligibility for autologous stem cell
transplantation. Prior CART therapy is allowed. A total of 480 pts
will be randomized 1:1 to receive either SC epcoritamab or up to 4
cycles of biweekly treatment with intravenous (IV) RGemOx (8
doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks).
Epcoritamab will be given at the recommended phase 2 dose in 28
day cycles: weekly, biweekly, or monthly schedule depending on cy-
cle number. Treatment is administered until disease progression or
unacceptable toxicity. The primary endpoint is overall survival. Key
secondary endpoints include progressionfree survival, overall
response rate, duration of response, time to response, and safety. The
study is currently enrolling in Australia, Belgium, Denmark, France,
Spain, and will open for enrollment in additional countries
(NCT04628494).
EA previously submitted to ASCO 2021.
The research was funded by: Genmab A/S and AbbVie Inc.
Keywords: Ongoing Trials
Conflicts of interests pertinent to the abstract
C. Thieblemont
Consultant or advisory role: Celgene, Roche, Novartis, and Janssen
Honoraria: Gilead Sciences, Novartis, Celgene, Roche, and Janssen
Research funding: Roche
Educational grants: Novartis, Roche, Gilead Sciences, and Janssen
M. R. Clausen
Consultant or advisory role: Janssen, AbbVie, Gilead
Educational grants: Gilead, AbbVie
C. P. Fox
Honoraria: Genmab, Roche, Celgene/BMS, AbbVie, Morphosys,
Incyte, Atrarbio, Astrazeneca, Takeda, Gilead
Other remuneration: Research Grants: Roche, AbbVie, Takeda, Gilead
P. Lugtenburg
Other remuneration: Takeda, Servier, Roche, Genmab, Celgene,
Regeneron, Incyte
251 |PHASE 3 RANDOMIZED STUDY OF LONCASTUXIMAB
TESIRINE PLUS RITUXIMAB VERSUS IMMUNOCHEMOTHERAPY
IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B
CELL LYMPHOMA LOTIS5
C. CARLOSTELLA
1
, Y. Linhares
2
, M. D. Gandhi
3
, M. Chung
4
, H.
Adamis
5
, D. Ungar
6
, M. Hamadani
7
1
Humanitas Clinical and Research Center IRCCS, and Humanitas
University, Department of Oncology and Hematology, Rozzano, Milan,
Italy,
2
Miami Cancer Institute, Baptist Health, Medical Oncology, Miami,
USA,
3
Virginia Cancer Specialists, Medical Oncology, Gainesville, USA,
4
The Oncology Institute of Hope and Innovation, Hematology/Oncology,
Downey, USA,
5
ADC Therapeutics SA, Clinical Development, Epalinges,
Switzerland,
6
ADC Therapeutics America, Inc, Clinical Development,
Murray Hill, USA,
7
Medical College of Wisconsin, Division of Hematology
and Oncology, Milwaukee, USA
Introduction: Patients (pts) with diffuse large Bcell lymphoma
(DLBCL) for whom frontline therapy is unsuccessful and who are
ineligible for autologous stem cell transplantation (SCT) have poor
outcomes with salvage therapy. Singleagent loncastuximab tesirine
(Lonca), an antibodydrug conjugate comprising a humanized anti
CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine
dimer toxin, showed antitumor activity and manageable toxicity in
pts with relapsed/refractory (R/R) Bcell nonHodgkin lymphoma in a
Phase 1 trial (Hamadani et al. Blood 2020; blood.2020007512) and in
pts with R/R DLBCL in a Phase 2 trial (Caimi et al. Blood 2020; 136
(Suppl 1):35–37).
Rituximab (R) is part of standard immunochemotherapy for
DLBCL, both as frontline therapy and in subsequent treatments.
LOTIS5 aims to evaluate Lonca +R (LoncaR) versus (vs) standard
immunochemotherapy of R +gemcitabine +oxaliplatin (RGemOx) in
pts with R/R DLBCL.
Methods: This is a Phase 3 randomized, openlabel, 2part, 2arm,
multicenter study (NCT04384484). A nonrandomized safety runin
(Part 1) will compare the safety of LoncaR with previous safety
data for Lonca after the first 20 pts have completed Cycle 1. Part 2
will be started if no significant increase in toxicity occurs; 330 pts
will be randomized 1:1 to receive LoncaR or RGemOx.
The primary objective of the study is to evaluate the efficacy of
LoncaR vs RGemOx. The primary endpoint is progressionfree
survival by independent review. Secondary endpoints include over-
all survival; objective response rate; complete response rate; dura-
tion of response; frequency and severity of adverse events; changes
from baseline in safety laboratory and clinical variables; concentra-
tion and pharmacokinetic parameters of Lonca (conjugated and total
antibody, and unconjugated warhead); immunogenicity; and changes
in patientreported outcomes. Timetoevent endpoints will be
assessed for the intenttotreat population using a stratified log rank
test. The dosing regimen of LoncaR in both parts of the study will be
150 µg/kg Lonca +375 mg/m
2
R every 3 weeks (Q3W) for 2 cycles
and then 75 µg/kg Lonca +375 mg/m
2
R for 6 cycles. The dose
regimen of RGemOx in Part 2 will be 375 mg/m
2
R, 1000 mg/m
2
Gem, and 100 mg/m
2
Ox Q2W for 8 cycles.
Key inclusion criteria include age 18 years; pathologic diagnosis
of DLBCL (including pts with DLBCL transformed from indolent lym-
phoma) or highgrade Bcell lymphoma with MYC and BCL2 and/or
BCL6 rearrangements; 1 line of prior systemic therapy; not a candi-
date for SCT; and measurable disease per 2014 Lugano Classification.
The study opened in September 2020 and enrollment is ongoing.
The trial design was presented at 62nd American Society of
Hematology Annual Meeting and Exposition, December 5–8, 2020.
342
-
SUPPLEMENT ABSTRACTS
Encore abstract previously submitted to ASH 2020 (before
enrollment started); current abstract submitted to ASCO and EHA
2021.
© 2021 American Society of Clinical Oncology, Inc. Reused with
permission. This abstract was accepted and previously presented at
the 2021 ASCO Annual Meeting. All rights reserved.
The research was funded by: The research was funded by ADC
Therapeutics SA
Keywords: Aggressive Bcell nonHodgkin lymphoma, Combination
Therapies, Ongoing Trials
Conflicts of interests pertinent to the abstract
C. CARLOSTELLA
Consultant or advisory role: Sanofi, ADC Therapeutics, Roche, Kar-
yopharm Therapeutics, Celgene/BristolMyers Squibb, Incyte
Honoraria: BristolMyers Squibb, Merck Sharp & Dohme, Janssen
Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead Sciences
Research funding: ADC Therapeutics, Sanofi, Roche
Educational grants: Roche, Janssen, Takeda, ADC Therapeutics
M. D. Gandhi
Consultant or advisory role: GSK
H. Adamis
Employment or leadership position: Fresenius Kabi BioSim, ADC
Therapeutics
D. Ungar
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
M. Hamadani
Consultant or advisory role: MedImmune, Cellerant Therapeutics,
Janssen, Incyte, Pharmacyclics, ADC Therapeutics, Puma Biotech-
nology, Verastem
Honoraria: Celgene
Research funding: Takeda, Spectrum Pharmaceuticals, Otsuka US,
Astellas Pharma, Genzyme
Other remuneration: Genzyme (Speaker's bureau), Celgene
(Speaker's bureau), AstraZeneca (Speaker's bureau)
252 |ESCALADE: A PHASE 3 STUDY OF ACALABRUTINIB IN
COMBINATION WITH RCHOP FOR PATIENTS 65Y WITH
UNTREATED NONGERMINAL CENTER BCELL–LIKE DIFFUSE
LARGE BCELL LYMPHOMA
L. H. Sehn
1
, B. Kahl
2
, M. Matasar
3
, G. Lentz
4
, K. Izutsu
5
, W. Zhao
6
,
L. Tao
7
, R. Calvo
8
, P. L. Zinzani
9
1
BC Cancer Centre for Lymphoid Cancer, Medical Oncology, Vancouver,
Canada,
2
Washington University in St. Louis, Oncology, St. Louis, Missouri,
USA,
3
Memorial Sloan Kettering Cancer Center, Medical Oncology Service,
New York, New York, USA,
4
University Hospital Münster, Medicine A
Haematology and Oncology, Münster, Germany,
5
National Cancer Center
Hospital, Hematology, Tokyo, Japan,
6
Shanghai Institute of Haemato
oncology, Hematology, Shanghai, China,
7
AstraZeneca, Biostatistics, South
San Francisco, California, USA,
8
AstraZeneca, Clinical Development He-
matology, R&D Oncology, Gaithersburg, Maryland, USA,
9
Institute of
Hematology “Seràgnoli” University of Bologna, Experimental, Diagnostic
and Specialty Medicine DIMES, Bologna, Italy
Background: Rituximab, cyclophosphamide, doxorubicin, vincristine,
and prednisone (RCHOP) remains the standard of care for diffuse
large Bcell lymphoma (DLBCL). Although most patients (pts) can
be cured, 35–40% will experience relapsed/refractory disease,
leading to poor outcomes in the majority of pts. Covalent irre-
versible Bruton tyrosine kinase inhibitors (BTKi) have shown
higher responses in pts with nongerminal center Bcell–like (non
GCB) DLBCL than with GCB DLBCL. In untreated nonGCB DLBCL
pts, the phase 3 PHOENIX study (Younes et al. J Clin Oncol.
2019;37:128595) showed that addition of the BTKi ibrutinib to R
CHOP (RCHOPI) did not improve outcomes in the intenttotreat
population. However, pts age <60y treated with RCHOPI had
significantly improved progressionfree survival (PFS) and overall
survival (OS) compared with those receiving RCHOP alone. Aca-
labrutinib (A) is a secondgeneration BTKi with enhanced kinase
selectivity and potential for better efficacy and tolerability than
firstgeneration BTKis. There is a strong rationale for combining A
with RCHOP in pts with untreated DLBCL, and safety of A +R
CHOP has been shown in a phase 1b/2 study (Davies et al. ASH
2020). The aim of this study is to determine if the addition of A to
RCHOP leads to improved PFS in pts age 65y with untreated
nonGCB DLBCL.
Methods: ESCALADE (ACELY312; NCT04529772) is a phase 3,
randomized, global, doubleblind study of A vs placebo in combi-
nation with RCHOP for treatment of newly diagnosed nonGCB
DLBCL. The study is recruiting adults 18y and 65y with previ-
ously untreated DLBCL stage II–IV disease with a Revised Inter-
national Prognostic Index (RIPI) score of 2–5. Prior to
randomization, all pts will receive an initial RCHOP cycle (cycle 1)
as standardofcare treatment to prevent delays in therapy initia-
tion. Based on central Gene Expression Profile (GEP) testing per-
formed after enrollment, pts with nonGCB DLBCL (activated Bcell
like or unclassified) will be randomized into 2 arms to receive A 100
mg twice daily plus RCHOP or placebo plus RCHOP from cycle 2
to cycle 6 followed by 2 additional cycles of rituximab +A or pla-
cebo (cycles 7 and 8). All pts will receive primary prophylaxis with
granulocyte colonystimulating factors accompanying all RCHOP
cycles. The study aims to randomize 600 pts (300 per arm). The
primary objective is to evaluate whether the addition of A to R
CHOP will prolong PFS. Secondary endpoints include eventfree
survival, complete response rate, OS, pharmacokinetics, and
safety. Key exclusion criteria are central nervous system involve-
ment, primary mediastinal lymphoma, highgrade Bcell lymphoma,
diagnosis or treatment of malignancy other than DLBCL, and history
of indolent lymphoma. Approximately 250 sites globally will enroll
pts. Enrollment began in Q3 of 2020.
SUPPLEMENT ABSTRACTS
-
343
EA previously submitted to ASCO and EHA 2021.
The research was funded by: Acerta Pharm, a member of the
AstraZeneca Group
Keywords: Aggressive Bcell nonHodgkin lymphoma, Molecular
Targeted Therapies, Ongoing Trials
Conflicts of interests pertinent to the abstract
L. H. Sehn
Consultant or advisory role: Celgene, AbbVie, Seattle Genetics, TG
Therapeutics, Janssen, Amgen, Roche/Genentech, Gilead Sciences,
Lundbeck, Amgen, Apobiologix, Karyopharm Therapeutics, Kite
Pharma, Merck, Takeda, Teva, AstraZeneca, Acerta Pharma, Mor-
phosys, Incyte, Debiopharm Group, SandozNovartis, Genmab,
Verastem
Honoraria: Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences,
JanssenOrtho, Karyopharm Therapeutics, Kite Pharma, Lundbeck,
Merck, Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Ther-
apeutics, AstraZeneca, Acerta Pharma, Morphosys, Incyte, Debio-
pharm Group, SandozNovartis, Verastem, Genmab, AstraZeneca
Research funding: Roche/Genentech, Teva
B. Kahl
Consultant or advisory role: Celgene, AbbVie, Pharmacyclics, Acerta
Pharma, ADC Therapeutics, Genentech, Roche, BeiGene, Bayer, MEI
Pharma, Kite/Gilead, MorphoSys, Janssen, Karyopharm Therapeutics,
Teva, BMS, Molecular Templates, Incyte
Research funding: Genentech, Acerta Pharma, ADC Therapeutics,
Celgene
Educational grants: Celgene, Juno Therapeutics, Genentech/Roche,
AbbVie, Millenium, Seattle Genetics
M. Matasar
Consultant or advisory role: Genentech, Bayer, Merck, Juno Thera-
peutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi San-
kyo, Takeda;
Stock ownership: Merck
Honoraria: Genentech, Roche, Glaxosmithkline, Bayer, Pharmacy-
clics, Janssen, Seattle Genetics, Immunovaccine Technologies, Takeda
Research funding: Genentech, Roche, Glaxosmithkline, IGM Bio-
sciences, Bayer, Pharmacyclis, Janssen, Rocket Medical, Seattle GE-
netics, Immunovaccine Tech
Educational grants: Genentech, Roche, Seattle Genetics, Bayer
Other remuneration: Expert Testimony: Bayer
G. Lentz
Consultant or advisory role: Roche/Genentech, JanssenCilag,
BristolMyers Squibb, Bayer, Novartis, Celgene, MorphoSys, Astra-
Zeneca, Gilead Sciences
Honoraria: JanssenCilag, Bayer, Celgene, Roche/Genentech, Astra-
Zeneca, BMS, MorphoSys, Gilead Sciences, Novartis, AbbVie
Research funding: JanssenCilag, Roche/Genentech, AstraZeneca,
Aquinox Pharmaceuticals, Bayer, MorphoSys, Gilead Sciences, Vera-
stem, AGIOS
Educational grants: JanssenCilag, Celegene, AstraZeneca, Roche/
Genentech,
Other remuneration: Expert Testimony: MorphoSys
K. Izutsu
Consultant or advisory role: Bayer, Celgene, AstraZeneca, Ono
Pharmaceutical, Kyowa Kirin
Honoraria: Takeda, Chugai Pharma, Eisai, Janssen, AbbVie, Novartis,
MSD, Sumitomo Dainippon Pharma, Ono Pharmaceutical, Mundi-
pharma, HUYA Bioscience International, AstraZeneca, Bayer, BMS,
Kyowa Kirin, Fujifilm, Celgene, Daiichi Sankyo, Allergan
Research funding: Eisai, Chugai Pharma
L. Tao
Employment or leadership position: AstraZeneca
R. Calvo
Employment or leadership position: AstraZeneca
Stock ownership: AstraZeneca
P. L. Zinzani
Consultant or advisory role: Verastem, Celltrion, Gilead, Janseen
Cilag, BMS, Servier, Sandoz, MSD, TG Therapeutics, Takeda, Roche,
Eusapharma, Kwoya Kirin, Sanofi, ADC Therapteutics
Other remuneration: Speakers’ Bureau Verastem, Celltrion, Gilead,
JanseenCilag, BMS, Servier, MSD, TG Therapeutics, Takeda, Roche,
Eusapharma, Kyowa Kirin
253 |A PHASE III TRIAL OF GLOFITAMAB PLUS GEMCITABINE
AND OXALIPLATIN (GEMOX) VS RITUXIMAB PLUS GEMOX FOR
RELAPSED/REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA
M. Hertzberg
1
, M. Ku
2
, O. Catalani
3
, B. Althaus
4
, S. Simko
4
, G. P.
Gregory
5
1
Prince of Wales Hospital, Department of Hematology, Sydney, Australia,
2
St.Vincent's Hospital, The University of Melbourne, Department of
Haematology, Melbourne, Australia,
3
F. HoffmannLa Roche Ltd, Statis-
tics, Basel, Switzerland,
4
Genentech, Inc., Product Development Hema-
tology, South San Francisco, USA,
5
School of Clinical Sciences at Monash
Health, Monash University, Department of Clinical Haematology, Mel-
bourne, Australia
Introduction: Prognosis is poor for patients with relapsed/refractory
(R/R) diffuse large Bcell lymphoma (DLBCL), particularly those who
are ineligible for autologous stem cell transplant (ASCT) or who
relapse after secondline therapy (Gisselbrecht C, et al. Br J Hae-
matol 2018). While chimeric antigen receptor therapies have shown
favorable response rates in R/R DLBCL, convenient offtheshelf
options are needed, especially for patients with rapidly progressing
disease (Sermer D, et al. Blood Adv 2020). Glofitamab is a fulllength,
humanized immunoglobulin G1 bispecific antibody with two regions
that bind to CD20 (B cells) and one region that binds to CD3 (T cells).
In an ongoing Phase I study in patients with R/R nonHodgkin
344
-
SUPPLEMENT ABSTRACTS
lymphoma, glofitamab monotherapy has induced high response rates
with a manageable safety profile (NCT03075696; Hutchings M, et al.
ASH 2020). Rituximab in combination with GemOx (RGemOx) is
widely used for patients with R/R DLBCL who are not eligible for
ASCT (Mounier N, et al. Haematologica 2013).
Methods: GO41944 (NCT04408638) is a Phase III, openlabel, ran-
domized trial designed to evaluate the safety and efficacy of glofi-
tamab plus gemcitabine and oxaliplatin (glofitGemOx) vs RGemOx
in patients with R/R DLBCL. Eligible patients must be aged 18 years,
have histologically confirmed DLBCL (excluding transformed indolent
disease, and highgrade Bcell lymphoma (BCL) with MYC and BCL2
and/or BCL6 rearrangements), and have received 1 prior systemic
therapies; patients who have failed only one prior line of therapy
must not be eligible for highdose chemotherapy followed by ASCT.
Prior treatment with GemOx, RGemOx or a CD20xCD3 bispecific
antibody is not permitted. Patients are randomized 2:1 to receive up
to eight 21day cycles of either glofitGemOx (intravenous [IV], fol-
lowed by up to four cycles of glofitamab monotherapy) or RGemOx
(IV). A single dose of obinutuzumab is administered seven days prior
to the first glofitamab administration. Randomization is stratified by
number of prior lines of therapy and outcome of last systemic ther-
apy (relapsed vs refractory). The primary objective is overall survival
from time of randomization. Secondary efficacy objectives include
progressionfree survival, complete and overall response rates,
duration of response, and time to deterioration in physical func-
tioning and fatigue, and in lymphoma symptoms. Safety objectives
comprise rate of adverse events, change from baseline in targeted
vital signs and clinical laboratory test results, and tolerability. Phar-
macokinetic, immunogenicity and biomarker endpoints will also be
explored. The study started on February 17, 2021; an estimated
enrollment of 270 patients by the study completion date of March
2022 is anticipated.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: F. HoffmannLa Roche Ltd/Genentech,
Inc. Thirdparty medical writing assistance, under the direction of the
authors, was provided by Katie Buxton, PhD, of Ashfield MedComms,
an Ashfield Health company, and was funded by F. HoffmannLa
Roche Ltd/Genentech, Inc.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Ongoing Trials
Conflicts of interests pertinent to the abstract
M. Hertzberg
Consultant or advisory role: Takeda, Gilead, F. HoffmannLa Roche
Ltd, MSD
Honoraria: F. HoffmannLa Roche Ltd, Janssen, Takeda, Bristol
Myers Squibb
Research funding: F. HoffmannLa Roche Ltd, Janssen, GSK
M. Ku
Consultant or advisory role: F. HoffmannLa Roche Ltd, Antengene
Research funding: Karyopharm
O. Catalani
Employment or leadership position: F. HoffmannLa Roche Ltd
B. Althaus
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
S. Simko
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
G. P. Gregory
Consultant or advisory role: F. HoffmannLa Roche Ltd, Novartis/
Sandoz, Janssen, Gilead
Honoraria: F. HoffmannLa Roche Ltd
Research funding: F. HoffmannLa Roche Ltd, BeiGene, MSD, AbbVie,
Janssen
Educational grants: F. HoffmannLa Roche Ltd, Novartis
Other remuneration: Speakers' bureau: F. HoffmannLa Roche Ltd;
Expert testimony: Janssen
254 |BRENTUXIMAB VEDOTIN IN COMBINATION WITH
LENALIDOMIDE AND RITUXIMAB IN SUBJECTS WITH RELAPSED
OR REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA (DLBCL)
(TRIAL IN PROGRESS)
N. L. Bartlett
1
, C. A. Yasenchak
2
, K. K. Ashraf
3
, W. N. Harwin
4
, R. B.
Sims
5
, G. S. Nowakowski
6
1
Washington University School of Medicine, Division of Oncology, St.
Louis, Missouri, USA,
2
Willamette Valley Cancer Institute and Research
Center/US Oncology Research, Medical Oncology, Hematology,
Springfield, Oregon, USA,
3
Hematology and Oncology Associates of
Alabama, Medical Oncology, Hematology, Birmingham, Alabama, USA,
4
Sarah Cannon Research Institute, Hematology and Oncology, Fort
Meyers, Florida, USA,
5
Seagen Inc., Clinical Development, Bothell,
Washington, USA,
6
Mayo Clinic, Division of Hematology, Rochester,
Minnesota, USA
Introduction: The majority of patients (pts) with relapsed/refractory
(R/R) diffuse large Bcell lymphoma (DLBCL) who relapse after HSCT
or CART, or who are not candidates for HSCT or CART have poor
outcomes and are in need of novel therapies. Brentuximab vedotin
(BV) is a CD30directed ADC and preclinical data provide a strong
rationale for combining BV, lenalidomide, and rituximab in the
treatment of R/R DLBCL. In addition, in a phase 1 trial in which 37
pts with R/R DLBCL were treated with BV +lenalidomide, the ORR
was 56.7% (73.3% in CD30+pts; manuscript in preparation). The
median duration of remission was 13.2 months in pts with a CR or
PR and 11.7 months in pts with CR, PR, or stable disease >6 months.
The PFS and median OS were 11.2 months and 14.3 months,
respectively and results were similar in the CD30+and CD30 <1%
groups. The clinical activity and manageable safety profiles of
BV, lenalidomide, and rituximab as single agents, make the combi-
nation a potentially viable option in multiply relapsed and heavily
pretreated pts.
SUPPLEMENT ABSTRACTS
-
345
Methods: This is a randomized, doubleblind, placebocontrolled,
activecomparator, multicenter phase 3 study designed to evaluate the
efficacy of BV vs placebo, in combination with lenalidomide +ritux-
imab, in subjects with R/R DLBCL (EudraCT: 202000268633). Prior
to randomization, there will be a safety and PK runin period where 6
pts will receive BV, lenalidomide +rituximab, and safety and PK will be
evaluated after the first cycle of treatment; 6/6 subjects have been
enrolled.
Key eligibility criteria include: pts aged 18 with R/R DLBCL
with an eligible subtype; 2 prior lines of therapy and have relapsed,
declined, or are ineligible for stem cell transplant, or chimeric antigen
receptor Tcell (CART) therapy; ECOG 0 to 2; fluorodeoxyglucose
avid disease by PET and bidimensional measurable disease of at
least 1.5 cm by CT.
Patients (n =400) will be randomized 1:1 to receive either BV or
placebo in combination with lenalidomide +rituximab and will be
stratified by CD30 expression (positive [1%] versus <1%), prior
allogeneic or autologous stem cell transplant therapy (received or not),
prior CART therapy (received or not), and cell of origin (GCB or non
GCB).
The primary endpoints are PFS per BICR in the ITT and CD30+
populations. Key secondary endpoints are OS in the ITT and CD30+
populations, and ORR per BICR. Other secondary endpoints include
CR rate, duration of response, and safety and tolerability of the
combination. Disease response will be assessed by BICR and the
investigator according to the Lugano Classification Revised Staging
System. Radiographic disease evaluations, including contrast
enhanced CT scans and PET, will be assessed at baseline, then
every 6 weeks from randomization until Week 48, then every 12
weeks. PET is not required after CR is achieved.
The trial is currently enrolling and will be open in 16 countries.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: Seagen Inc.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Combination
Therapies, Ongoing Trials
Conflicts of interests pertinent to the abstract
N. L. Bartlett
Consultant or advisory role: Seagen Inc., Roche/Genentech, ADC
Therapeutics, BTG, Acerta Pharma
Research funding: Seagen Inc., Kite Pharma, Merck, BristolMyers
Squibb, Celgene, Immune Design, Forty Seven, Janssen, Pharmacy-
clics, Millennium, ADC Therapeutics, Autolus, Roche/Genentech,
Pfizer, Affirmed Therapeutics
C. A. Yasenchak
Consultant or advisory role: BeiGene
Stock ownership: Karyopharm Therapeutics
Honoraria: Seagen Inc., Takeda
Research funding: Seagen Inc.
W. N. Harwin
Research funding: Sarah Cannon Research Institute
R. B. Sims
Employment or leadership position: Seagen Inc.
G. S. Nowakowski
Consultant or advisory role: Celgene, MorphoSys, Genentech, Selvita,
Debiopharm Group, Kite/Gilead
Research funding: Celgene, NanoString Technologies, MorphoSys
255 |COPANLISIB IN COMBINATION WITH RITUXIMAB
BENDAMUSTINE IN PATIENTS WITH RELAPSEDREFRACTORY
DLBCL: A MULTICENTRIC PHASE II TRIAL OF THE FONDAZIONE
ITALIANA LINFOMI
M. Novo
1
, A. Castellino
2
, A. Chiappella
3
, G. Ciccone
4
, M. Balzarotti
5
,
A. Di Rocco
6
, M. Spina
7
, U. Vitolo
1
1
FPOIRCCS Candiolo Cancer Institute, Multidisciplinary Oncology
Outpatient Clinic, Candiolo (TO), Italy,
2
Santa Croce e Carle Hospital,
Hematology Unit, Cuneo, Italy,
3
Fondazione IRCCS Istituto Nazionale dei
Tumori di Milano, Division of Hematology and Stem Cell Transplantation,
Milano, Italy,
4
Azienda OspedalieroUniversitaria Città della Salute e della
Scienza di Torino, Unit of Clinical Epidemiology and CPO, Torino, Italy,
5
Humanitas Clinical and Research Hospital IRCCS , Hematology Unit,
Rozzano (Milano), Italy,
6
Università La Sapienza, Department of Trans-
lational and Precision Medicine, Roma, Italy,
7
National Cancer Institute,
Division of Medical Oncology, Aviano, Italy
Introduction: Diffuse large B cell lymphoma (DLBCL) is a curable
disease in 5060% of cases with frontline immunochemotherapy.
Salvage strategies for relapsed/refractory (R/R) DLBCL are able to
cure 4050% of patients (pts), and include high dosechemotherapy +
autologous stem cell transplant (ASCT) and chimeric antigen receptor
Tcells (CART), the latter allowed after 2 prior lines of treatment in
pts with no major comorbidities. Thus, new strategies for R/R DLBCL
unresponsive or ineligible to ASCT or CART are warranted. Ritux-
imab +bendamustine (RB) is active in R/R DLBCL but response is
usually of short duration. Copanlisib is an intravenous panclass I
PI3K inhibitor with predominant activity against PI3K‐α and ‐δ iso-
forms, active as monotherapy in indolent lymphomas (iNHL) and
DLBCL with overall response rates (ORR) of 59% and 25%, respec-
tively (NCT01660451)(NCT02391116). Transient hyperglycemia and
transient hypertension are the most frequent treatmentemergent
adverse events. The association of copanlisib +RB (CopaRB)
showed a safe toxicity profile when tested on R/R iNHL
(NCT02626455). The aim of this trial is to evaluate safety and effi-
cacy of CopaRB followed by copanlisib maintenance in R/R DLBCL
not eligible or relapsed after ASCT or CART.
Methods: This is a multicentric openlabel single arm, single stage,
phase II trial. An estimated 81 pts will be enrolled, from 30 centers in
Italy. Main inclusion criteria are pts aged 18 affected by DLBCL
(including denovo DLBCL, DLBCL transformed by iNHL and high
grade lymphoma) R/R after 3 previous lines of therapy, ineligible
or R/R to ASCT or CART, ECOG performance status 02. Primary
346
-
SUPPLEMENT ABSTRACTS
mediastinal B cell lymphoma are excluded. Treatment include an in-
duction phase with six 28day cycles of copaRB (copanlisib 60 mg
intravenously on day (D) 1, D8 and D15, rituximab 375 mg/m
2
on D1,
bendamustine 90 mg/m
2
on D1D2) followed by a maintenance
phase of twelve 28day cycles of copanlisib 60 mg given on D1 and
D15 (Figure). The primary endpoint is progression free survival (PFS),
with an expected improvement of 12month PFS from 20% to 35%.
Secondary endpoints include overall survival, ORR, complete
response rate, duration of response and rate of response improve-
ment during maintenance. Exploratory analysis will include correla-
tion between outcome and cell of origin, MYC, BCL2 and BCL6
overexpression and rearrangements, and mutational analysis of
selected genes possibly involved in predicting response to copanlisib.
The expected study duration from first pts's enrollment to last pts's
last visit is approximately 4 years. The recruitment started in
November 2020 and at March 12th 8/81 pts have been enrolled.
Results for this study are not yet available. Clinical trial information:
NCT04433182
The research was funded by: The study is sponsored by Fondazione
Italiana Linfomi. The study is partially supported by Bayer
Keywords: Aggressive Bcell nonHodgkin lymphoma, Combination
Therapies, Ongoing Trials
No conflicts of interests pertinent to the abstract.
256 |A PHASE II STUDY OF ANTIPD1 SINTILIMAB IN
COMBINATION WITH CHIDAMIDE AND AZACITIDINE IN
REFRACTORY AND RELAPSED PERIPHERAL TCELL LYMPHOMA
Z. Ying
1
, Y. Song
1
, X. Wang
1
, N. Lin
1
, Y. Xie
1
, T. Du
1
, Y. Tang
1
, J. Zhu
1
1
Peking University Cancer Hospital & Institute, Key Laboratory of
Carcinogenesis and Translational Research (Ministry of Education/Beijing),
Department of Lymphoma, Beijing, China
Background: Peripheral Tcell lymphomas (PTCLs) are a highly
heterogeneous group of aggressive malignant lymphomas, usually
exhibit a poor prognosis, with a 5year survival <50%, the risk of
relapse remains quite high and relapsed or refractory (R/R) patients
have been shown to have a very dismal outcome. Immunotherapy
with antiPD1 antibodies may help the body's immune system attack
the cancer, and may interfere with the ability of tumor cells to grow
and spread. So far the largest study (Gxplore002) including 102
patients with R/R PTCL showed that antiPD1 antibody is safe and
has promising activity with overall response rate (ORR) of 40.4%.
However, the depth of remission and long term prognosis are not
satisfied with complete response rate (CRR) of 14.6% and the median
progressionfree survival of 2.7 months. Combination therapy is a
potential strategy to increase the efficacy. Epigenetic agents may
promote effect of antiPD1 antibody by stimulating antigen pre-
sentation, enhancing the migration of T cells to the tumor microen-
vironment, restoring T cell activation. These rationales support the
combination of antiPD1 antibody and epigenetic agents. Therefore,
the combination of sintilimab (antiPD1 antibody) and chidamide
(histone deacetylase inhibitors, HDACi), azacitidine (hypomethylating
agents, HMA) may have potent synergy in treating patients with
relapsed or refractory PTCLs.
Methods: This is a singlearmphase II clinical trial for patients with
relapsed or refractory PTCLs. Patients with at least one line of
standard therapy are required. Prior HDACi or PD1/PDL1 anti-
bodies or HMA is allowed. Patients with CNS disease or cutaneous T
cell lymphoma are excluded. Eligible patients will be treated with
sintilimab (200 mg IV Q3W on day 1) in combination with chidamide
(30 mg PO BIW on d1 and d4) and azacitidine (100 mg SC Q3W days
17). Cycles repeat every 3 weeks for up to 24 months in the absence
of disease progression, death, unacceptable toxicity, hematopoietic
stem cell transplantation, withdrawal of informed consent, other
reasons specified in the protocol or the decision of the researcher.
After completion of study treatment, participants are followed up at
90 days for safety and then every 90 days for survival. The study
intends to enroll approximately 30 patients. Considering the safety of
patients, the first 6 patients will be recruited slowly, if a DLT is
observed in 2 of 6 patients, the investigators will decide to reduce
the dose of chidamide to 20 mg, otherwise, all patients use 30 mg
SUPPLEMENT ABSTRACTS
-
347
chidamide. The primary objective is ORR; the secondary objectives
are CRR, duration of response (DOR), progressionfree survival (PFS),
overall survival(OS) and adverse events; the exploratory objective is
the correlation of clinical response with the expression of PDL1,
CD4, CD8, CD68 in tumor environment. Clinical trial information:
NCT04052659
The research was funded by: Innovent Biologics Inc.
Keywords: Combination Therapies, Immunotherapy, Aggressive T
cell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
257 |AN OPENLABEL TRIAL OF ORAL CA4948 AN IRAK4
INHIBITOR COMBINED WITH IBRUTINIB IN ADULT PATIENTS
WITH RELAPSED OR REFRACTORY HEMATOLOGIC
MALIGNANCIES
E. Joffe
1
, R. Ramchandren
2
, G. Nowakowski
3
, A. Rosenthal
4
, H. W.
Tun
5
, M. Lunning
6
, M. D. Mead
7
, E. Martinez
8
, R. von Roemeling
8
, L.
Leslie
9
1
Memorial Sloan Kettering Cancer Center, Hematology Oncology
Lymphoma Services, NY, New York, USA,
2
University of Tennessee
Medical CenterUniversity Cancer Specialists, Hematology, Medical
Oncology, Knoxville, Tennessee, USA,
3
Mayo ClinicMinnesota, Rochester,
MN, Hematology Cancer Center, Rochester, Minnesota, USA,
4
Mayo
ClinicArizona, Hematology, Phoenix, Arizona, USA,
5
Mayo Clinic, Florida,
Hematology OncologyCaner Center, Jacksonville, Florida, USA,
6
Uni-
versity of Nebraska, Division of Oncology & Hematology, Omaha,
Nebraska, USA,
7
University of California Los AngelesSanta Monica
Medical Center, Medicine, Hematology and Oncology, Santa Monica ,
California, USA,
8
Curis, Clinical Development, Lexington, Massachusetts,
USA,
9
John Theurer Cancer Center, Hackensack, NJ, Hematology
Oncology, Hackensack, New Jersey, USA
Introduction: Interleukin1 receptorassociated kinase 4 (IRAK4) is
essential for tolllike receptor (TLR) and interleukin1 receptor (IL1R)
signaling in immune cells including B lymphocytes. It forms the Myd-
dosome complex with the myeloid differentiation primary response
88 (MYD88) adaptor protein, driving maximal activation of Nuclear
Factor Kappa B (NFkB) causing inflammatory and immune responses
and tumor promotion. Preclinical studies demonstrated the role of
IRAK4 activation as a driver of secondary, adaptive tumor resistance
and tumor survival mechanisms that could be delayed or reversed. CA
4948 is a novel small molecule, oral inhibitor of IRAK4. When com-
bined with the Bruton kinase (BTK) inhibitors, it has shown invivo
synergy in Bcell NonHodgkin Lymphoma (NHL) models. CA4948
was previously reported to be well tolerated and active as mono-
therapy in heavily pretreated relapsed / refractory NHL.
Methods: An ongoing trial of CA4948 in combination with ibrutinib
in relapsed or refractory hematologic malignancies (NCT03328078).
Rationale: Demonstration of synergy between CA4948 and ibruti-
nib. The study is designed as follows:
Part A: Dose escalation monotherapy, results from the phase 1 study
were presented at American Society of Hematology (ASH) 2020.
Part A2 Combination: Dose escalation with a 3 +3 design. Primary
objectives: Safety/tolerance, maximum tolerated dose (MTD), rec-
ommended phase 2 dose (RP2D). Secondary objectives: pharmaco-
kinetics (PK) and preliminary efficacy. Exploratory objectives:
Correlation with MYD88L265P mutation status
Part B Combination: A basket design of 4 expansion cohorts with a
Simon 2Stage approach, applied to each cohort.
Primary objective: Efficacy; complete response (CR), objective
response rate (ORR) and duration of response (DOR). Secondary
objectives:Safety and tolerance, progression free survival (PFS) and
populationPK. Exploratory objective: biomarkers correlations.
Inclusion criteria for Part A2, NHL subtypes (WHO 2016):
Follicular lymphoma, marginal zone lymphoma (MZL), mantle cell
lymphoma (MCL), diffused large Bcell lymphoma (DLBCL), chronic
lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma
(SLL), primary or secondary central nervous system lymphoma (CNS),
Waldenström macroglobulinemia (WM) and lymphoplasmacytic
lymphoma (LPL). Part B: cohorts 13 include BTKinhibitor naïve
patients of similar histologies to part A2, cohort 4 includes patients
with adaptive ibrutinib resistance.
Exclusions for both Parts A2 and B: Significant acute or chronic un-
resolved toxicity from prior therapy; serious comorbidities.
Summary: CA4948 is a novel oral IRAK4 inhibitor of the TLR/
myddosome pathway that showed preclinical synergistic activity in
combination with ibrutinib. Clinical safety, tolerance, and preliminary
efficacy in selected NHL cohorts are being studied.
Keywords: Ongoing Trials
No conflicts of interests pertinent to the abstract.
258 |EPSTEINBARR VIRUSDRIVEN DISEASES: A
MULTINATIONAL, MULTICOHORT, OPENLABEL PHASE 2 STUDY
TO ASSESS THE EFFICACY AND SAFETY OF TABELECLEUCEL
USING AN ADAPTIVE STUDY DESIGN
S. Choquet
1
, J. A. PérezSimón
2
, N. Worel
3
, S. Chaganti
4
, R. Dinavahi
5
,
N. GuzmanBecerra
6
, W. Navarro
5
, Y. Sun
6
, L. Gamelin
7
1
Hôpital PitiéSalpêtrière, Hématologie, Paris, France,
2
Hospital
Universitario Virgen del Rocío, Hematología, Sevilla, Spain,
3
Medical
University of Vienna, Blutgruppenserologie and Transfusionsmedizin,
Vienna, Austria,
4
Queen Elizabeth Hospital Birmingham, Hematology,
Birmingham, UK,
5
Atara Biotherapeutics, Clinical Sciences, South San
Francisco, USA,
6
Atara Biotherapeutics, Biostatistics, Thousand Oaks,
USA,
7
Atara Biotherapeutics, Drug Safety and Pharmacovigilance, South
San Francisco, USA
Introduction: Epstein–Barr virus (EBV) infection is associated with a
variety of lifethreatening malignant and nonmalignant diseases. In
immunocompromised individuals, impaired immunosurveillance can
result in uncontrolled EBV infection. This may lead to EBV
+
348
-
SUPPLEMENT ABSTRACTS
immunodeficiencyassociated lymphoproliferative disorders (AI
LPD), EBV
+
sarcomas, or EBVassociated endorgan damage. EBV
driven LPDs are a heterogeneous group of diseases with variable
clinical and pathologic features, including primary IALPD (EBV
+
PID
LPD), acquired IALPD (EBV
+
AIDLPD) often associated with HIV
infection, and posttransplant lymphoproliferative disorder (EBV
+
PTLD). In addition, EBV infection of mesenchymal cells can cause
sarcomas, including leiomyosarcoma (EBV
+
sarcoma). In rare in-
stances, EBV viremia (ie persistent EBV infection) is associated with
lifethreatening complications such as chronic active EBV (CAEBV)
and hemophagocytic lymphohistiocytosis (HLH).
Tabelecleucel is an investigational, offtheshelf, allogeneic Tcell
immunotherapy without genetic modification. Initial safety and effi-
cacy data showed that tabelecleucel was well tolerated and displayed
clinical activity in patients with each of the EBVdriven diseases
being proposed in this study (ATA129EBV205; Kurlander et al. Ann
Oncol 2018; Nikiforow et al. Blood 2020; Torno et al. Blood 2020;
Prockop et al. J Clin Invest 2020). A Phase III study of tabelecleucel
for solidorgan or allogeneic hematopoietic cell transplant patients
with EBV
+
PTLD after failure of rituximab or rituximab plus
chemotherapy (NCT03394365) is ongoing.
Methods: This is a multinational, multicohort, openlabel, single arm
per cohort, Phase II study to assess the efficacy and safety of tabe-
lecleucel in patients with EBVassociated diseases (ATA129EBV
205; NCT04554914). Participants with EpsteinBarr virus (EBV)
driven diseases where standard firstline therapy is not appropriate
or who are relapsed/refractory to standard firstline therapy will be
enrolled in the following cohorts: EBV+AIDLPD, EBV+PIDLPD,
EBV+sarcoma (including leiomyosarcoma [LMS]), CAEBV/HLH,
EBV +PTLD with central nervous system (CNS) involvement and
firstline inappropriate EBV+PTLD. Prior to screening, the avail-
ability of tabelecleucel from an existing inventory based on an
appropriate HLA restriction and allele profile will be confirmed.
Tabelecleucel will be administered in cycles lasting 35 days. At the
end of each cycle, responses will be assessed per diseasespecific
criteria. An adaptive twostage design will be used for each cohort
in this study, and for each, a maximum of 8 patients will be enrolled in
stage 1. The decision to move to stage 2 enrollment for any given
cohort will be based on an analysis of the first 8 evaluable patients in
the cohort using investigator's assessment (per diseasespecific
response criteria).
The research was funded by: Atara Biotherapeutics.
Keywords: Ongoing Trials
Conflicts of interests pertinent to the abstract
S. Choquet
Consultant or advisory role: Atara Biotherapeutics
J. A. PérezSimón
Honoraria: Atara Biotherapeutics
S. Chaganti
Consultant or advisory role: Atara Biotherapeutics
R. Dinavahi
Employment or leadership position: Atara Biotherapeutics
Stock ownership: Atara Biotherapeutics
N. GuzmanBecerra
Employment or leadership position: Atara Biotherapeutics
Stock ownership: Atara Biotherapeutics
W. Navarro
Employment or leadership position: Atara Biotherapeutics
Stock ownership: Atara Biotherapeutics
Y. Sun
Employment or leadership position: Atara Biotherapeutics
Stock ownership: Atara Biotherapeutics
L. Gamelin
Employment or leadership position: Atara Biotherapeutics
Stock ownership: Atara Biotherapeutics
259 |A PHASE II STUDY OF ACALABRUTINIB IN
COMBINATION WITH RCHOP CHEMOTHERAPY PRIOR TO
AUTOLOGOUS STEM CELL TRANSPLANTATION IN PREVIOUSLY
UNTREATED MANTLE CELL LYMPHOMA
D. Villa
1
, D. W. Scott
1
, R. Morin
1
, H. Nakamura
1
, J. F. Larouche
2
, M.
Cheung
3
, N. Johnson
4
, M. Elemary
5
, M. M. Keating
6
, P. Tonseth
7
, K.
Zukotynski
8
, S. Mayo
9
, R. Goswami
10
, R. Laister
11
, J. Kuruvilla
11
1
BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,
2
Centre
Hospitalier Universitaire de Québec, Hôpital de l’EnfantJésus, Quebec
City, Canada,
3
Sunnybrook Health Sciences Centre, Department of
Hematology, Toronto, Canada,
4
Jewish General Hospital, Department of
Hematology, Montreal, Canada,
5
Saskatchewan Cancer Agency,
Saskatoon Cancer Centre, Saskatoon, Canada,
6
Nova Scotia Cancer
Centre, QEII Health Sciences Centre, Halifax, Canada,
7
BC Cancer,
Department of Functional Imaging, Vancouver, Canada,
8
McMaster
University, Departments of Radiology and Medicine, Hamilton, Canada,
9
University of Toronto, Lawrence S. Bloomberg Faculty of Nursing,
Toronto, Canada,
10
Sunnybrook Health Sciences Centre, Department of
Laboratory Medicine and Pathobiology, Toronto, Canada,
11
University
Health Network, Princess Margaret Cancer Centre, Toronto, Canada
Introduction: Rituximab in combination with cytotoxic chemotherapy
followed by autologous stem cell transplantation (ASCT) and main-
tenance rituximab (MR) is a standard treatment strategy in young
and fit patients with mantle cell lymphoma (MCL). Various chemo-
therapy regimens can be used as part of induction therapy, but there
is no single standard of care.
Frontline therapy can be improved by adding novel agents such
as Bruton tyrosine kinase inhibitors (BTKi) which are active in
relapsed/refractory MCL and can be safely combined with immu-
nochemotherapy. In the European Triangle study (NCT02858258)
ibrutinib is given for 3 weeks with RCHOP, but not with RDHAP,
SUPPLEMENT ABSTRACTS
-
349
which means patients receive intermittent BTKi exposure before
ASCT. Continuous, uninterrupted BTKi could maximize the benefit of
frontline therapy given that responses are known to develop over
time.
Acalabrutinib achieves BTK inhibition at lower doses than ibruti-
nib and also has less offtarget BTK inhibition. We hypothesize that
combining continuous acalabrutinib with RCHOP may result in a
tolerable, outpatient, highly active regimen allowing a high proportion
of patients to proceed with ASCT and/or achieve MRD negativity.
Methods: NCT04566887 is a phase II, nonrandomized, openlabel,
singlearm study conducted across 7 academic centres in Canada.
Patients 18 years of age with previously untreated MCL, perfor-
mance status 02, adequate organ function and considered fit for
ASCT will be included.
Patients receive 6 cycles of RCHOP at standard doses plus aca-
labrutinib 100 mg twice per day orally (Figure 1). Responding patients
proceed with ASCT and subsequently receive MR and acalabrutinib for
a total of 2 years. Patients who do not proceed to ASCT for reasons
other than progressive disease also receive MR and acalabrutinib.
The primary endpoint is the complete response rate after 6 cy-
cles of induction with centrally reviewed PET/CT using the Lugano
Classification for Malignant Lymphoma. Secondary endpoints include
frequency of adverse events, response rates according to the Inter-
national Working Group consensus response evaluation criteria in
lymphoma (RECIL 2017), rate of minimal residual disease (MRD)
negativity prior to ASCT and at any time during study treatment,
eventfree survival, and overall survival.
MRD testing will be performed on serial peripheral blood and
bone marrow aspirates using a panel that covers commonly mutated
MCL genes, including the CCND1 breakpoint region. Serial peripheral
blood samples will also be used for other correlative studies including
analyses of circulating tumor DNA and microRNA. Diagnostic tumor
tissue will be centrally analyzed using the MCL35 assay. Patient re-
ported outcomes will be assessed using the FACTLym and EORTC
QLQC30 questionnaires.
The sample size is n =54. The first patient was enrolled in March
2021. Accrual is expected to continue for 23 years.
Keywords: Molecular Targeted Therapies, Indolent nonHodgkin
lymphoma, Ongoing Trials
Conflicts of interests pertinent to the abstract
D. Villa
Consultant or advisory role: Janssen, Nanostring
Research funding: AstraZeneca (research funding to the institution)
J. Kuruvilla
Research funding: AstraZeneca (research funding to the institution)
260 |FIRSTLINE IBRUTINIB +VENETOCLAX TREATMENT FOR
MANTLE CELL LYMPHOMA IN OLDER PATIENTS OR THOSE
WITH TP53 MUTATION: A NEW OPENLABEL ARM OF THE
PHASE 3 PCYC1143 SYMPATICO STUDY
W. Jurczak
1
, C. Tam
2
, K. Eckert
3
, J. Lin
4
, J. K. Neuenburg
3
, M. L.
Wang
5
1
Maria SklodowskaCurie National Institute of Oncology, Department of
Clinical Oncology, Kraków, Poland,
2
Peter MacCallum Cancer Centre & St.
Vincent's Hospital, Department of Haematology, Melbourne, Australia,
3
Pharmacyclics LLC, an AbbVie Company, Oncology Division, Sunnyvale,
California, USA,
4
Pharmacyclics LLC, an AbbVie Company, Department of
Biostatistics, Sunnyvale, California, USA,
5
MD Anderson Cancer Center,
Department of Lymphoma Myeloma, Houston, Texas, USA
Introduction: Ibrutinib is a oncedaily Bruton tyrosine kinase (BTK)
inhibitor approved in the US for patients with mantle cell lymphoma
(MCL) who have received 1 prior therapy. Having demonstrated
overall response rates of 68–72% and complete response (CR) rates
of 19–21%, singleagent ibrutinib received accelerated US approval
for MCL (Wang NEJM 2013; Dreyling Lancet 2016). Venetoclax, a B
cell lymphoma 2 (BCL2) inhibitor, is approved in the US for patients
with previously untreated acute myeloid leukemia and for patients
with CLL who received 1 prior therapy. Singleagent venetoclax
demonstrated a CR rate of 21% in patients with MCL (Davids J Clin
Oncol 2017). In preclinical models, dual inhibition of BTK pathways by
ibrutinib and BCL2 pathways by venetoclax resulted in synergistic
antitumor activity (Zhao Br J Haematol 2015). In the phase 2 AIM
study conducted in patients with MCL, combination treatment with
ibrutinib plus venetoclax resulted in a best response of CR in 71% of
24 patients. Importantly, in patients with a TP53 mutation, who are
considered chemoinsensitive, the CR rate was 50%, including one
previously untreated patient (Tam NEJM 2018). The objective of this
new, openlabel arm of the ongoing phase 3 SYMPATICO study is to
evaluate firstline ibrutinib plus venetoclax in patients 65 years and
in patients <65 years with a TP53 mutation, populations that have an
unmet need for chemotherapyfree regimens and for whom limited
treatment options exist.
Methods: Approximately 75 patients with MCL will be enrolled in
this new openlabel arm of the ongoing phase 3 SYMPATICO trial.
Eligibility criteria include patients with pathologically confirmed,
previously untreated MCL who are either 65 years or 18–64 years
with a TP53 mutation. All patients must have measurable disease
and an Eastern Cooperative Oncology Group performance status of
0–2. Patients will be ineligible if they have received prior treatment
with a BTK or BCL2 inhibitor or have blastoidvariant MCL or a
history or current evidence of CNS lymphoma. Patients will receive
350
-
SUPPLEMENT ABSTRACTS
oral, oncedaily ibrutinib 560 mg plus venetoclax in a 5week ramp
up to 400 mg. Treatment will continue for up to 24 months, after
which venetoclax will be discontinued in all patients and single
agent ibrutinib will continue until progressive disease or unaccept-
able toxicity. The primary objective is to evaluate the CR rate;
secondary objectives include additional efficacy evaluations, safety,
and pharmacokinetics. Status: The new arm of the SYMPATICO
study conducted in previously untreated patients is currently
enrolling at multiple global sites; anticipated completion is in 2022.
As of Jan 11, 2021, the study is recruiting only those patients with
known TP53 mutations, including those aged 65 and older, for
enrollment.
EA previously submitted to regional or national meetings (up to
1000 attendees).
The research was funded by: Pharmacyclics LLC, an AbbVie Company
Keywords: Aggressive Bcell nonHodgkin lymphoma, Immuno-
therapy, Ongoing Trials
Conflicts of interests pertinent to the abstract
W. Jurczak
Consultant or advisory role: Acerta, Astra Zeneca, BeiGene, Epizyme,
Janssen, Loxo, Novartis, and Sandoz
Research funding: Acerta, Bayer, BeiGene, Janssen, MeiPharma,
Merck, Pharmacyclics LLC, an AbbVie Company, Roche, Takeda, and
TG Therapeutics
C. Tam
Consultant or advisory role: AbbVie, BeiGene, Janssen, Loxo
Oncology, and Roche
Honoraria: AbbVie, BeiGene, Janssen, Novartis, and Pharmacyclics
LLC, an AbbVie Company
Research funding: AbbVie and Janssen
K. Eckert
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: AbbVie
J. Lin
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: AbbVie
J. K. Neuenburg
Employment or leadership position: Pharmacyclics LLC, an AbbVie
Company
Stock ownership: AbbVie
M. L. Wang
Consultant or advisory role: AstraZeneca, Celgene, Guidepoint
Global, InnoCare, Janssen, Juno, Kite Pharma, Loxo Oncology, Mor-
eHealth, Nobel Insights, Oncternal, Pharmacyclics LLC, an AbbVie
Company, and Pulse Biosciences
Honoraria: AstraZeneca, Beijing Medical Award Foundation, Dava
Oncology, Janssen, Lu Daopei Medical Group, OMI, OncLive, Phar-
macyclics LLC, an AbbVie Company, and Targeted Oncology
Research funding: Acerta Pharma, AstraZeneca, BioInvent, Celgene,
Janssen, Juno Therapeutics, Kite Pharma, Loxo Oncology, Molecular
Templates, Oncternal, Pharmacyclics LLC, an AbbVie Company,
VelosBio, and Verastem
Educational grants: Acerta, AstraZeneca, BioInvent, Celgene, Jans-
sen, Juno Therapeutics, Kite Pharma, Loxo Oncology, Molecular
Templates, Oncternal, Pharmacyclics LLC, an AbbVie Company,
VelosBios, and Verastem
261 |THREE PHASE 1/2, OPENLABEL STUDIES OF CEREBLON
E3 LIGASE MODULATOR (CELMOD)BASED REGIMENS IN
NEWLY DIAGNOSED (ND) OR RELAPSED/REFRACTORY (R/R)
NONHODGKIN LYMPHOMA (NHL)
F. Morschhauser
1
, G. S. Nowakowski
2
, G. Cartron
3
, V. Kesanakurthy
4
,
A. Gkasiamis
5
, P. Patah
6
, R. Delarue
7
, T. Wang
8
, J. Li
9
, D. Xian
10
, C. P.
Fox
11
, P. Martin
12
1
Université de Lille, Centre Hospitalier Universitaire de Lille. ULR 7365,
GRITA Groupe de Recherche sur les formes Injectables et les
Technologies Associées, Département d'Hématologie, Lille, France,
2
Mayo Clinic Hospital, Department of Hematology, Rochester,
Minnesota, USA,
3
CHU de Montpellier Hôpital SaintEloi, Départe-
ment d'Hématologie clinique, Montpellier, France,
4
Bristol Myers
Squibb, Global Drug Development, Princeton, New Jersey, USA,
5
Bristol
Myers Squibb, Global Drug Development, Neuchâtel, Switzerland,
6
Bristol Myers Squibb, Global Drug Development, Princeton, New Jer-
sey, USA,
7
Bristol Myers Squibb, Global Drug Development, Neuchâtel,
Switzerland,
8
Bristol Myers Squibb, Global Biometrics and Data Sci-
ences, Princeton, New Jersey, USA,
9
Bristol Myers Squibb, Global Bio-
metrics and Data Sciences, Princeton, New Jersey, USA,
10
Bristol Myers
Squibb, Global Biometrics and Data Sciences, Princeton, New Jersey,
USA,
11
Nottingham University Hospitals NHS Trust, Department of
Clinical Haematology, Nottingham, UK,
12
Weill Cornell Medicine, Divi-
sion of Hematology/Oncology, New York, New York, USA
Introduction: Lenalidomide (LEN)based therapies have shown ac-
tivity in NHL. These include LEN +antiCD20 agent (rituximab or
obinutuzumab) in follicular lymphoma (Morschhauser et al. N Engl J
Med 2018; Morschhauser et al. Lancet Haematol 2019) and in R/R
NHL (Wang et al. Leukemia 2013), as well as LEN +tafasitamab in R/R
diffuse large Bcell lymphoma (DLBCL; Salles et al. Lancet Oncol
2020). Additionally, LEN +RCHOP demonstrated significantly
improved progressionfree survival (PFS) versus RCHOP in ND
DLBCL (Nowakowski, Hong et al. J Clin Oncol 2021), and a positive
trend in PFS in ABC subtype of ND DLBCL (Nowakowski, Chiappella
et al. J Clin Oncol 2021). Early results also showed clinical activity of
LEN +polatuzumab vedotin/obinutuzumab in R/R follicular lym-
phoma (Diefenbach et al. ASH 2019). Iberdomide (IBER; CC220) and
CC99282 are novel oral CELMoDs that induce degradation of
SUPPLEMENT ABSTRACTS
-
351
Ikaros/Aiolos, resulting in immunomodulatory and antitumor effects.
IBER has 20x higher cereblonbinding affinity than LEN, leading to
significantly faster degradation of target substrates (Matyskiela et al.
J Med Chem 2018), and is active in NHL cell lines. CC99282 displays
efficacy in DLBCL cell lines independent of cell of origin. Thus, the
use of CELMoDs may provide more effective therapies for ND and R/
R NHL. Here we describe 3 dosefinding and safety studies (1 for
NHL, 2 for aggressive Bcell lymphoma [aBCL]) that will assess
CELMoDs in combination with antiCD20 agents, RCHOP, or other
agents in NHL.
352
-
SUPPLEMENT ABSTRACTS
Methods: CC220NHL001, CC220DLBCL001, and CC220
DLBCL002 are phase 1/2, openlabel, multicenter, doseescalation
(part 1) and doseexpansion (part 2) studies. Eligible patients (pts)
aged 18 years must have ND aBCL (Study DLBCL001), or R/R
lymphoma (Study NHL001) or R/R aBCL (Study DLBCL002) with
2 prior lines of therapy, as well as measurable disease per Lugano
2014 classification, and ECOG performance status of 0–2. Primary
objectives are to determine the maximum tolerated dose and rec-
ommended phase 2 dose (RP2D) of IBER (all studies) or CC99282
(Study DLBCL001 only), as well as to evaluate safety/tolerability
at RP2D (Study DLBCL001 only) and efficacy (Study DLBCL002
only). Secondary objectives include safety, pharmacokinetics, and
efficacy. In Study NHL001, pts will be enrolled in treatment (tx)
cohorts based on lymphoma subtype (Figure). In part 1 of each study,
pts will receive the assigned tx, including IBER or CC99282 at
escalating dose levels; in part 2, pts will receive CELMoDbased tx at
the RP2D determined in part 1 (Figure). All tx will continue until the
planned number of cycles is reached or progression/unacceptable
toxicity.
EA previously submitted to ASCO 2021.
The research was funded by: Bristol Myers Squibb
Keywords: Aggressive Bcell nonHodgkin lymphoma, Indolentnon
Hodgkin lymphoma, OngoingTrials
Conflicts of interests pertinent to the abstract
F. Morschhauser
Consultant or advisory role: Roche, Genentech, Servier
Other remuneration: Speakers' bureau: Roche, Gilead, Janssen.
Board of directors or advisory committee: Roche, Gilead, Abbvie,
Celgene, Epizyme
G. Cartron
Consultant or advisory role: Roche, Celgene
Honoraria: Jansen, Sanofi, Novartis, Gilead, Roche, Celgene
V. Kesanakurthy
Employment or leadership position: Bristol Myers Squibb
A. Gkasiamis
Employment or leadership position: Bristol Myers Squibb
P. Patah
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
R. Delarue
Employment or leadership position: Celgene, a Bristol Myers Squibb
company
Stock ownership: Bristol Myers Squibb
T. Wang
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb, Vir Biotechnology
J. Li
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
Educational grants: Bristol Myers Squibb
D. Xian
Employment or leadership position: Bristol Myers Squibb
C. P. Fox
Consultant or advisory role: Abbvie, AstraZeneca, Atarabio, Bristol
Myers Squibb/Celgene, Gilead, Janssen, Incyte, Roche, Takeda
Honoraria: Abbvie, Atarabio, Bristol Myers Squibb/Celgene, Janssen,
Incyte, Roche, Takeda
Research funding: Abbvie, Gilead, Roche, Takeda
Educational grants: Abbvie, Bristol Myers Squibb/Celgene, Janssen,
Roche, Takeda
P. Martin
Consultant or advisory role: ADCT, AstraZeneca, Bayer, BeiGene,
Bristol Myers Squibb, Cellectar, Epizyme, Gilead, Incyte, Janssen,
Karyopharm, Merck, Regeneron, Takeda, Teneobio, Verastem
262 |COASTAL: A PHASE 3 STUDY OF THE PI3KδINHIBITOR
ZANDELISIB WITH RITUXIMAB (R) VERSUS
IMMUNOCHEMOTHERAPY IN PATIENTS WITH RELAPSED
INDOLENT NONHODGKIN'S LYMPHOMA (INHL)
W. Jurczak
1
, P. L. Zinzani
2
, D. Cunningham
3
, S. Yavrom
4
, W. Huang
5
, I.
Gorbatchevsky
6
, V. Ribrag
7
1
Maria SklodowskaCurie National Research Institute of Oncology, He-
matology, Krakow, Poland,
2
Institute of Hematology "L. e A. Seràgnoli",
Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Bologna,
Italy,
3
Royal Marsden Hospital, NHS Foundation Trust, Haematology
Oncology, London, UK,
4
MEI Pharma Inc., Clinical Development, San
Diego, USA,
5
MEI Pharma Inc., Biostats, San Diego, USA,
6
MEI Pharma
Inc., Clinical Development, San Diego, USA,
7
Institut Gustave Roussy,
Hematology, Villejuif, France
Background: Patients (pts) with iNHL treated with frontline immu-
nochemotherapy may benefit from an alternative, chemotherapy
free regimen at relapse. Zandelisib, a potent, selective, and struc-
turally differentiated oral PI3Kδinhibitor, achieved an 87% response
rate, with median duration of response not reached in iNHL when
given as a monotherapy or in combination with R. A low rate (<10%)
of Grade 3 immunemediated adverse events of special interest
associated with PI3kδinhibitors is observed in patients administered
zandelisib on an intermittent schedule (IS) (JCO 2020 38:15_suppl,
8016). An openlabel, phase 2 study (TIDAL, NCT03768505) of
zandelisib as monotherapy is ongoing in pts with relapsed/refractory
follicular lymphoma (FL) and marginal zone lymphoma (MZL).
Methods: The COASTAL study is a randomized, openlabel,
controlled multicenter phase 3 trial to investigate the safety and
efficacy of zandelisib in combination with R versus standard
SUPPLEMENT ABSTRACTS
-
353
immunochemotherapy in pts with iNHL. Key eligibility criteria: adults
with relapsed or refractory FL or MZL who received 1 prior lines of
therapy which must have included an antiCD20 antibody in combi-
nation with chemotherapy or lenalidomide (L); at least one bi
dimensionally measured lesion >1.5 cm; adequate bone marrow,
renal and hepatic function; ECOG performance status score of 0 to 1.
Key exclusion criteria: histologically confirmed diagnosis of FL grade
3b or transformed disease; administration of 2 prior immunoche-
motherapy regimens; prior PI3K inhibitor therapy; known lympho-
matous involvement of the central nervous system. Subjects will be
randomized 1:1 to receive Rzandelisib or immunochemotherapy (R
CHOP or RB) and stratified by type and number of prior treatment
regimens, histology, and duration of treatmentfree interval after last
therapy. Zandelisib will be given in a 28day cycle comprising of daily
dosing for 2 cycles followed by IS dosing on days 17 or each 28day
subsequent cycle for a duration of 2 years. Rituximab or immu-
nochemotherapy will be given for a total of 6 cycles. Disease
response will be assessed by an Independent Response Review
Committee according to the modified Lugano Classification. Radio-
graphic tumor assessment will be performed approximately every 12
weeks for the first 9 months, every 16 weeks for the next 12 months,
and every 24 weeks thereafter. The primary efficacy endpoint is
progressionfree survival. The major secondary endpoints include
ORR, complete response rate, overall survival, and safety. The trial
will enroll approximately 534 pts in 200 sites globally and will begin
enrollment in mid2021 (NCT04745832).
EA previously submitted to ASCO and EHA 2021.
The research was funded by: MEI Pharma Inc.
Keywords: Indolent nonHodgkin lymphoma, Molecular Targeted
Therapies, Ongoing Trials
No conflicts of interests pertinent to the abstract.
263 |INMIND: A PHASE 3 STUDY OF TAFASITAMAB +
LENALIDOMIDE AND RITUXIMAB VS PLACEBO +
LENALIDOMIDE AND RITUXIMAB FOR RELAPSED/REFRACTORY
FOLLICULAR OR MARGINAL ZONE LYMPHOMA
K. Hübel
1
, C. W. Scholz
2
, S. Luminari
3
, A. Salar
4
, B. E. Wahlin
5
, A. K.
Gopal
6
, C. Bonnet
7
, M. Trneny
8
, S. Paneesha
9
, O. Manzke
10
, F.
Seguy
10
, D. Li
11
, L. H. Sehn
12
1
University Hospital Cologne, Department of Internal Medicine I Oncology
and Hematology, Cologne, Germany,
2
Vivantes Klinikum Am Urban,
Department of Hematology and Oncology, Berlin, Germany,
3
Azienda
USLIRCCS di Reggio Emilia, Hematology Unit, Reggio Emilia, Italy,
4
Hospital del MarIMIM, Department of Haematology, Barcelona, Spain,
5
Unit of Hematology, Karolinska Institute, Department of Medicine,
Stockholm, Sweden,
6
University of Washington Medicine, Division of
Medical Oncology, Seattle, Washington, USA,
7
Centre Hospitalier Uni-
versitaire, University of Liège, Clinical Hematology, Liège, Belgium,
8
First
Faculty of Medicine, Charles University, General Hospital, First Depart-
ment of Medicine, Prague, Czech Republic,
9
University Hospitals
Birmingham NHS Foundation Trust, Hematology, Birmingham, UK,
10
Incyte Biosciences International Sàrl, Clinical Development, Morgues,
Switzerland,
11
Incyte Corporation, Biostatistics, Wilmington, Delaware,
USA,
12
BC Cancer Centre for Lymphoid Cancer and The University of
British Columbia, Division of Medical Oncology, Vancouver, Canada
Background: Most patients (pts) with the indolent nonHodgkin
lymphoma (NHL) subtypes follicular lymphoma (FL) or marginal
zone lymphoma (MZL) respond to firstline treatment but relapse is
common, and there is no single standard treatment for pts with
relapsed/refractory (R/R) FL or MZL. Tafasitamab is an Fc
engineered humanized monoclonal antibody (mAb) against CD19
which is broadly expressed in FL and MZL, and regulates Bcell
proliferation via Bcell receptor signaling. In preclinical studies,
tafasitamab has shown activity against NHL cell lines in combination
with rituximab (antiCD20 mAb) and lenalidomide (LEN). Tafasitamab
monotherapy has shown promising clinical activity in a phase 2a
study in pts with R/R NHL (NCT01685008), with an ORR of 29% (n/N
=10/34) in pts with FL and 33% (n/N =3/9) in pts with MZL. In an
ongoing phase 2, singlearm study (LMIND, NCT02399085), tafasi-
tamab plus LEN followed by tafasitamab alone demonstrated an ORR
of 57.5% (n/N =46/80), CR of 40% (n/N =32/80) and median DOR
of 34.6 months (95% CI: 26.1–NR), in pts with R/R diffuse large Bcell
lymphoma (FDA approved indication). These preclinical and clinical
observations from phase 2 trials suggest a potential clinical benefit of
tafasitamab plus LEN and rituximab for pts with R/R FL or MZL.
Methods: This phase 3 doubleblind, placebocontrolled, randomized
study is designed to investigate whether tafasitamab plus LEN and
rituximab provides improved clinical benefit compared with LEN and
rituximab in pts with R/R FL or R/R MZL. Pts will be randomized 1:1
to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28
day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) plus LEN (20
mg PO QD [10 mg PO QD if creatinine clearance 30 to <60 mL/
minute], days 1–21/ cycle for 12 cycles) and rituximab (375 mg/m
2
IV
on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or
placebo (0.9% saline solution IV) plus LEN and rituximab. The primary
study endpoint is PFS (investigator assessed [INV] by Lugano 2014
criteria) for pts with FL. Key secondary endpoints are PFS (INV) in
overall population (FL and MZL), PETCR rate (INV) at end of
treatment (4–8 weeks after last treatment) and OS in pts with FL.
Inclusion criteria include age 18 y, histologically confirmed FL
(grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented
R/R disease, 1 prior systemic antiCD20 therapy (including anti
CD20 refractory disease), ECOG PS 2, adequate systemic organ
function, and high tumor burden (per GELF criteria). Exclusion
criteria include prior rituximab plus LEN treatment, history of
radiotherapy for other diseases (25% of bone marrow), non-
hematologic malignancy, congestive heart failure (LVEF <50%),
active systemic infection, known CNS lymphoma, or severe immu-
nocompromised state. inMIND (NCT04680052, EudraCT2020
00440713) is currently enrolling pts; planned enrollment is 528 pts
with R/R FL and 60–90 pts with R/R MZL.
EA previously submitted to ASCO and EHA 2021.
354
-
SUPPLEMENT ABSTRACTS
The research was funded by: Incyte Corporation
Keywords: Indolent nonHodgkin lymphoma, Combination Therapies,
Ongoing Trials
Conflicts of interests pertinent to the abstract
K. Hübel
Consultant or advisory role: Celgene, EUSA, Gilead, Incyte, Roche,
Servier
C. W. Scholz
Consultant or advisory role: Roche
S. Luminari
Consultant or advisory role: Bristol Myers Squibb, Genmab, Jannsen,
Regeneron, Roche
A. Salar
Consultant or advisory role: Celgene, Janssen, and Roche
Research funding: Gilead
B. E. Wahlin
Consultant or advisory role: Roche
Research funding: Gilead
A. K. Gopal
Honoraria: Incyte, MorphoSys
C. Bonnet
Consultant or advisory role: Roche
M. Trneny
Consultant or advisory role: AbbVie, Amgen, BristolMyers Squibb,
Celgene, Gilead Sciences, Incyte, Janssen, MorphoSys, Roche, Takeda
Honoraria: AbbVie, Amgen, BristolMyers Squibb, Gilead Sciences,
Incyte, Janssen, MorphoSys, Roche, Takeda
Other remuneration: AbbVie, BristolMyers Squibb, Gilead Sciences,
Janssen, Roche, Takeda
S. Paneesha
Honoraria: Celgene, Roche
O. Manzke
Employment or leadership position: Incyte
Stock ownership: Incyte
F. Seguy
Employment or leadership position: Incyte
Stock ownership: Incyte
D. Li
Employment or leadership position: Incyte
Stock ownership: Incyte
L. H. Sehn
Consultant or advisory role: AbbVie, Acerta, Apobiologix, AstraZe-
neca, Celgene, Debiopharm, Genentech, Genmab, Gilead, Incyte,
Janssen, Karyopharm, Kite, Lundbeck, Merck, MorphoSys, Novartis,
Sandoz, Takeda, TG Therapeutics, Verastem, Roche, Seattle Genetics,
Teva
Research funding: Teva
264 |A PHASE 2 RANDOMIZED STUDY OF LONCASTUXIMAB
TESIRINE (LONCA) VERSUS (VS) IDELALISIB IN PATIENTS (PTS)
WITH RELAPSED OR REFRACTORY (R/R) FOLLICULAR
LYMPHOMA (FL) LOTIS6
C. CarloStella
1
, J. Depaus
2
, B. T. Hess
3
, E. Kingsley
4
, P. L. Zinzani
5
, D.
Ungar
6
, V. Dai
6
, L. Wang
6
, K. M. Ardeshna
7
1
Humanitas Clinical and Research Center IRCCS, and Humanitas
University, Department of Oncology and Hematology, Rozzano, Milan,
Italy,
2
CHU UCL Namur site Godinne, Department of Hematology, Yvoir,
Belgium,
3
Medical University of South Carolina, Division of Hematology
and Medical Oncology, Department of Medicine, Charleston, USA,
4
Comprehensive Cancer Centers of Nevada, Las Vegas, USA,
5
IRCCS
Azienda OspedalieroUniversitaria di Bologna Istituto di Ematologia
"Seràgnoli" and Diagnostica e Sperimentale Università di Bologna,
Dipartimento di Medicina Specialistica, Bologna, Italy,
6
ADC Therapeutics
America, Inc, Clinical Development, Murray Hill, USA,
7
University College
London Hospitals NHS Foundation Trust, Department of Haematology,
London, UK
Introduction: Many pts with FL respond to firstline therapy, but
most have successive relapses and response duration shortens
after each relapse; FL is hence an area of substantial unmet
need. Singleagent Lonca, an antibody (Ab)drug conjugate
comprising a humanized antiCD19 monoclonal Ab conjugated to a
pyrrolobenzodiazepine dimer (PBD) toxin, showed antitumor ac-
tivity and manageable safety in R/R Bcell nonHodgkin lymphoma
eg, FL in a Phase 1 trial (ADCT402101) and in heavily pretreated
pts with R/R diffuse large Bcell lymphoma in a Phase 2 trial
(ADCT402201). Idelalisib is a phosphatidylinositol 3kinase in-
hibitor approved for pts with relapsed FL with 2 prior systemic
therapies.
The primary objective of this trial (NCT04699461; opened
in Spring 2021) is to assess the efficacy of Lonca vs idelalisib in
R/R FL.
Methods: Key inclusion criteria in the prospective, randomized, 2
arm, multicenter, openlabel, Phase 2 trial include: age 18 years;
pathologic FL diagnosis (Grade 1, 2, 3A); 2 prior therapy lines (1 of
which included an antiCD20 therapy); measurable disease as defined
by the 2014 Lugano Classification; and adequate organ function and
performance status. Pts will be randomized 2:1 to Lonca (intrave-
nously; 150 µg/kg every 3 weeks [Q3W] for 2 cycles then 75 µg/kg
Q3W for subsequent cycles) or idelalisib (oral; 150 mg twice daily),
based on time since last systemic therapy (ie, 2 years vs >2 years).
The followup period will be 3 years after treatment end. Pts can
continue therapy until disease progression, unacceptable toxicity, or
other discontinuation criteria.
SUPPLEMENT ABSTRACTS
-
355
Complete response rate (CRR; primary endpoint) per 2014
Lugano Classification, by central review, will be tested for the
intenttotreat population between treatment arms using the
Cochran–Mantel–Haenszel method adjusted for stratification fac-
tors from the randomization list. The trial is 99% powered for the
primary endpoint assuming a 55% CRR to Lonca and a 15% CRR
to idelalisib; the sample size for enrollment (150 pts) allows for a
robust safety data set. Secondary endpoints include overall
response rate (key secondary endpoint); progressionfree survival;
overall survival; duration of response; incidence and severity of
adverse events (AEs) and serious AEs; change from baseline in
laboratory values, vital signs, 12lead electrocardiogram, and
Eastern Cooperative Oncology Group performance status; con-
centration and pharmacokinetic parameters of Lonca total and
PBDconjugated Ab, and unconjugated warhead (SG3199); anti
drug Ab titers; and ptreported outcome (PRO) measures of
change from baseline in PROs (by EuroQol–5 Dimensions–5 Levels
and Functional Assessment of Cancer TherapyLymphoma) and,
incidence, severity, and interference of specific symptomatic
AEs from the PROs version of the Common Terminology Criteria
for AEs.
EA previously submitted to EHA 2021.
The research was funded by: ADC Therapeutics SA
Keywords: Indolent nonHodgkin lymphoma, Combination Therapies,
Ongoing Trials
Conflicts of interests pertinent to the abstract
C. CarloStella
Consultant or advisory role: Sanofi, ADC Therapeutics, Roche, Kar-
yopharm Therapeutics, Celgene/BristolMyers Squibb, Incyte
Honoraria: BristolMyers Squibb, Merck Sharp & Dohme, Janssen
Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead Sciences
Research funding: ADC Therapeutics, Sanofi, Roche
Educational grants: Roche, Janssen, ADC Therapeutics
J. Depaus
Consultant or advisory role: Takeda, Novartis, Janssen, AstraZeneca
B. T. Hess
Consultant or advisory role: ADC Therapeutics, Karyopharm
Therapeutics
Other remuneration: BristolMyers Squibb, AstraZeneca (both
speaker's bureau)
P. L. Zinzani
Consultant or advisory role: ADC Therapeutics, BristolMyers
Squibb, Celltrion, EUSA Pharma, Gilead Sciences, JanssenCilag,
Kyowa Kirin, Merck Sharp & Dohme, Roche, Sandoz, Sanofi, Servier,
Takeda, TG Therapeutics, Verastem Oncology
Other remuneration: Speaker's bureau: BristoMyers Squibb, Cellt-
rion, EUSA Pharma, Gilead, Sciences, JanssenCilag, Kyowa Kirin,
Merck Sharp & Dohme, Roche, Servier, Takeda, TG Therapeutics,
Verastem Oncology
D. Ungar
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
V. Dai
Employment or leadership position: ADC Therapeutics, SUNY
Research Foundation
Stock ownership: ADC Therapeutics
L. Wang
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
K. M. Ardeshna
Other remuneration: Autolus Therapeutics, Celgene
CART CELL THERAPY
265 |CARDIOVASCULAR EVENTS AMONG ADULT PATIENTS
WITH AGGRESSIVE BCELL LYMPHOMA TREATED WITH
STANDARD OF CARE AXICABTAGENE CILOLEUCEL AND
TISAGENLECLEUCEL
R. Steiner
1
, J. Banchs
2
, E. Koutroumpakis
2
, M. Becnel
1
, C. Gutierrez
3
,
P. Strati
1
, C. Pinnix
4
, L. Feng
5
, C. Claussen
1
, N. Palaskas
2
, K.
Karimzad
2
, S. Ahmed
1
, S. Neelapu
1
, E. Shpall
6
, M. Wang
1
, F. Vega
7
, J.
Westin
1
, L. Nastoupil
1
, A. Deswal
2
1
MD Anderson Cancer Center, Lymphoma & Myeloma, Houston, Texas,
USA,
2
MD Anderson Cancer Center, Cardiology, Houston, USA,
3
MD
Anderson Cancer Center, Critical Care & Respiratory Care, Houston,
Texas, USA,
4
MD Anderson Cancer Center, Radiation Oncology, Houston,
Texas, USA,
5
MD Anderson Cancer Center, Biostatistics, Houston, Texas,
USA,
6
MD Anderson Cancer Center, Stem Cell Transplantation, Houston,
Texas, USA,
7
MD Anderson Cancer Center, Hematopathology, Houston,
Texas, USA
Introduction: Standard of care (SOC) AntiCD19 chimeric antigen
receptor (CAR) Tcell therapies such as axicabtagene ciloleucel (axi
cel) and tisagenlecleucel (tisacel) are associated with cytokine
release syndrome (CRS) and immune cellassociated neurotoxicity
syndrome (ICANS).
There is limited information available about cardiovascular (CV)
events associated with SOC axicel or tisacel. In the clinical trials
leading to their FDA approval, patients with CV comorbidities, organ
dysfunction, or lower performance status were often not included.
An improved understanding of CV toxicities in the realworld setting
will better guide therapy selection and management of patients
receiving these cellular therapies.
Methods: We retrospectively reviewed the characteristics and out-
comes of adult patients with relapsed/refractory large Bcell lym-
phoma treated with SOC axicel or tisacel between 01/2018 and 4/
2020 at MD Anderson Cancer Center. Major adverse CV events
within 30 days after infusion (30d MACE) included arrhythmias
356
-
SUPPLEMENT ABSTRACTS
requiring intervention (ARI), new cardiomyopathy (NCMP), exacer-
bation of heart failure (HF), cerebrovascular accident (CVA),
myocardial infarction (MI), or CV death. MACE, CRS, and ICANS were
treated per institutional standards.
Results: Onehundred and sixtyfive patients were included in the
analysis, and baseline characteristics are shown in the Table. Overall,
16% of patients developed at least one 30d MACE: 60.6% ARI (atrial
fibrillation/flutter 40.7%, nonsustained ventricular tachycardia
40.7%), 12.1% EHF, 12.1% CVA, 6.1% MI, 6.1% NCMP, and one pa-
tient died due to MI. The first 30d MACE occurred in a median of 7
days (range 029) after CART cell infusion. Moreover, 6 patients had
one recurrence of 30d MACE (2 EHF, 2 ARI, and 2 CVA), and 3
SUPPLEMENT ABSTRACTS
-
357
patients experienced two recurrences of 30d MACE (1 ARI and 2
NCMP).
As displayed in the Table, age >60 years, baseline echocardio-
graphic diastolic dysfunction, earlier start of CRS, CRS grade 3,
long duration of CRS, and use of tocilizumab were significantly
associated with an increased risk of 30d MACE.
No association between timing and/or magnitude of Creactive
protein or ferritin peak and occurrence of MACE was observed.
After a median followup time of 16.2 months (range 14.319.1)
for censored observations, the occurrence of 30d MACE was not
significantly associated with progressionfree survival (PFS) (pvalue
=0.55, logrank test), or with overall survival (OS) (pvalue =0.52,
logrank test).
Conclusions: Our results suggest that the occurrence of 30d MACE
is more frequent among patients who are elderly, with baseline dia-
stolic dysfunction, early, severe and prolonged CRS, but had no sta-
tistically significant impact on PFS and OS. However, with limited
followup, larger prospective studies are needed, and multidisci-
plinary management of these patients is recommended.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Cellular
therapies
Conflicts of interests pertinent to the abstract
R. Steiner
Research funding: Rafael Pharmaceuticals
C. Gutierrez
Consultant or advisory role: Advisory Board for Legend Biotech &
Janssen (2020 and 2021)
P. Strati
Consultant or advisory role: Consultant for RocheGenentech
S. Ahmed
Research funding: Research funding from Seattle genetics and Tessa
therapeutics
S. Neelapu
Consultant or advisory role: consultant to Kite, a Gilead Company,
Merck, BristolMyers Squibb, Novartis, Celgene, Pfizer, Allogene
Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences,
Legend Biotech, Adicet Bio, Calibr, and Unum Therapeutics
Honoraria: received royalties from Takeda Pharmaceuticals,
Research funding: received research support from Kite, a Gilead
Company, BristolMyers Squibb, Merck, Poseida, Cellectis, Celgene,
Karus Therapeutics, Unum Therapeutics, Allogene Therapeutics,
Precision Biosciences, and Acerta
Other remuneration: intellectual property related to cell therapy
E. Shpall
Consultant or advisory role: Consultant on Scientific Advisory
Boards: Bayer HealthCare Pharmaceuticals, Novartis, Magenta,
Adaptimmune, Mesoblast, Axio
Honoraria: Honorarium: Magenta, Novartis, Bayer HealthCare
Pharmaceuticals
Other remuneration: License Agreements or Patents: Takeda (EJ
Shpall is listed as a coinventor on a provisional patent application on
Takeda that is owned by MD Anderson and licensed to Takeda.
Affimed
M. Wang
Consultant or advisory role: Consultancy InnoCare, Loxo Oncology,
Juno, Oncternal, CStone, AstraZeneca, Janssen, VelosBio,
Honoraria: Janssen, Acerta Pharma, OMI, Physicians Education Re-
sources, Dava Oncology, CAHON, Hebei Cancer Prevention Feder-
ation, Clinical Care Options, Mumbai Hematology Group, Anticancer
Association, Newbridge Pharmaceuticals.
Research funding: Research Funding Pharmacyclics, Janssen,
AstraZeneca, Celgene, Loxo Oncology, Kite Pharma, Juno, BioInvent,
VelosBio, Acerta Pharma, Oncternal, Verastem, Molecular Templates,
Lilly, Innocare.
F. Vega
Research funding: Research support from CRISP therapeutics
Other remuneration: Salary support from NCI/NIH R01 CA222918
J. Westin
Consultant or advisory role: Advisory: Kite, BMS, Novartis, ADC
Therapeutics, Iksuda, Genentech, AstraZeneca, Curis, Morphosys
Research funding: Clinical trial funding: Kite, BMS, Novartis, ADC
Therapeutics, Genentech, AstraZeneca, Curis, Morphosys, 47 Inc
L. Nastoupil
Honoraria: Honorarium: ADC Therapeutics, Bayer, BMS/Celgene,
Epizyme, Genentech, Gilead, Janssen, Novartis, Pfizer, TG
Therapeutics.
Research funding: Research funding: BMS/Celgene, Epizyme, Gen-
entech, Janssen, Novartis, Pfizer, Takeda, TG Therapeutics.
266 |PATIENTREPORTED QUALITY OF LIFE (QOL)
FOLLOWING TISAGENLECLEUCEL (TISACEL) INFUSION IN
ADULT PATIENTS (PTS) WITH RELAPSED/REFRACTORY
FOLLICULAR LYMPHOMA (R/R FL)
N. H. Fowler
1
, M. Dickinson
2
, J. MartinezLopez
3
, A. Kolstad
4
, S. J.
Schuster
5
, M. Dreyling
6
, M. Ghosh
7
, H. Harigae
8
, M. José Kersten
9
, E.
Bachy
10
, L. Popplewell
11
, J. C. Chavez
12
, P. J. Ho
13
, J. Butler
14
, K.
Kato
15
, B. von Tresckow
16
, A. J. M. Ferreri
17
, J. A. P. Simón
18
, P. E. M.
Patten
19
, C. Andreadis
20
, P. A. Riedell
21
, J. P. McGuirk
22
, L. J. Nas-
toupil
23
, T. Teshima
24
, F. Offner
25
, A. Petzer
26
, A. Viardot
27
, P. L.
Zinzani
28
, R. Malladi
29
, J. Zhang
30
, R. Tiwari
31
, V. Bollu
32
, A.
Masood
33
, C. Thieblemont
34
1
The University of Texas MD Anderson Cancer Center, Department of
LymphomaMyeloma, Houston, Texas, USA,
2
Royal Melbourne Hospital,
Peter MacCallum Cancer Centre, Melbourne, Australia,
3
Hospital 12 De
Octubre, Complutense University, CNIO, Madrid, Spain,
4
Oslo University
358
-
SUPPLEMENT ABSTRACTS
Hospital, Department of Oncology, Oslo, Norway,
5
University of Penn-
sylvania, Lymphoma Program, Philadelphia, Pennsylvania, USA,
6
LMU
Klinikum, Medizinische Klinik III, Munich, Germany,
7
University of Mich-
igan, Michigan Medicine, Ann Arbor, Michigan, USA,
8
Tohoku University
Hospital, Department of Hematology and Rheumatology, Sendai, Japan,
9
Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC,
Department of Hematology, Amsterdam, Netherlands,
10
Université
Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon, France,
11
City of
Hope National Medical Center, Department of Hematology & Hemato-
poietic Cell Transplantation, Duarte, California, USA,
12
Moffitt Cancer
Center, Department of Malignant Hematology, Tampa, Florida, USA,
13
Royal Prince Alfred Hospital and University of Sydney, Institute of
Haematology, Camperdown, Australia,
14
Royal Brisbane Hospital, Hae-
matology and Bone Marrow Transplant Unit, Herston, Australia,
15
Kyushu
University Hospital, Hematology, Oncology, & Cardiovascular Medicine,
Fukuoka, Japan,
16
University Hospital Essen, University of Duisburg
Essen, Clinic for Hematology and Stem Cell Transplantation, West German
Cancer Center, Essen, Germany,
17
IRCCS Ospedale San Raffaele,
Department of Oncohematology, Milan, Italy,
18
University Hospital Vir-
gen del Rocío, Instituto de Biomedicina de Sevilla (IBIS / CSIC / CIBER-
ONC), Universidad de Sevilla, Department of Hematology, Sevilla, Spain,
19
King's College Hospital and King's College London, Division of Cancer
Studies, London, UK,
20
University of California San Francisco, Helen Diller
Family Comprehensive Cancer Center, San Francisco, California, USA,
21
University of Chicago Medical Center, Department of Medicine, Chi-
cago, Illinois, USA,
22
University of Kansas Medical Center, Division of
Hematologic Malignancies and Cellular Therapeutics, Kansas City, Kansas,
USA,
23
The University of Texas MD Anderson Cancer Center, Department
of LymphomaMyeloma, Houston, Texas, USA,
24
Hokkaido University
Hospital, Department of Hematology, Sapporo, Japan,
25
UZ Gent,
Department of Hematology, Gent, Belgium,
26
Ordensklinikum Linz GmbH
Elisabethinen, Internal Medicine I, Linz, Austria,
27
University Hospital of
Ulm, Department of Internal Medicine III, Ulm, Germany,
28
University of
Bologna, Institute of Hematology “Seràgnoli”, Bologna, Italy,
29
Cambridge
University Hospitals NHS Foundation Trust, Centre for Clinical Haema-
tology, Cambridge, UK,
30
Novartis Pharmaceuticals Corporation, Global
Value and Access, East Hanover, New Jersey, USA,
31
Novartis Healthcare
Pvt. Ltd, Biostatistics, Hyderabad, India,
32
Novartis Pharmaceuticals
Corporation, Health Economics and Outcomes Research, East Hanover,
New Jersey, USA,
33
Novartis Pharmaceuticals Corporation, Clinical
Development, East Hanover, New Jersey, USA,
34
Hôpital SaintLouis
Université de Paris, Service d'HématologieOncologie, Paris, France
Introduction: Patientreported QoL is an important endpoint in the
singlearm phase II ELARA trial of tisacel, which has demonstrated
efficacy and favorable safety profiles in adult pts with r/r FL (Fowler
NH et al, ASH 2020). Here, we present patientreported QoL data
before and after tisacel infusion in ELARA.
Methods: Eligible pts (18 y) had r/r FL (grades 13A) after 2
lines of therapy or had failed autologous stem cell transplant
(autoSCT). Pts completed the Functional Assessment of Cancer
TherapyLymphoma (FACTLym) and Short Form36 Health Survey
v2 (SF36) at baseline, and at Months (Mo) 3 and 6 post tisacel
infusion. For both instruments, a change score >0 indicated
improved QoL.
Results: As of September 28, 2020, 98 pts were enrolled and 97
received tisacel (median followup, 10.6 mo); 75% of pts had pre-
viously received 3 prior lines of therapy and 36% had relapsed after
autoSCT. QoL instruments were completed by 79 pts (81%) at
baseline, including 69 pts who had a complete or partial response.
FACTLym and SF36 assessments were completed by 71 (74%) and
68 (71%) pts at Mo 3 and by 61 (65%) and 60 (64%) pts at Mo 6,
respectively. The FACTLym subscales showed improvement in the
emotional, functional, and physical domains. Furthermore, no dete-
rioration in the social/family domain by Mo 6 was reported, although
minimal clinically important differences of 2 were not reached.
Similarly, numeric improvement was observed in mean change scores
from baseline through Mo 3 for the SF36 mental health component
scores and through Mo 6 for the physical health component scores,
including general health, vitality, physical functioning, roleemotional,
and rolephysical. Overall, 40%49% of pts demonstrated clinically
meaningful improvements in QoL based on FACTLym and SF36
at Mo 3. Furthermore, 68%83% of pts’ QoL did not deteriorate
(Table). Similar trends were observed at Mo 6. Additionally, mean
SUPPLEMENT ABSTRACTS
-
359
change scores for FACTLym improved from baseline to Mo 3 and to
Mo 6.
Conclusions: These results demonstrate that clinically meaningful
improvements in QoL were observed in pts post tisacel infusion.
The research was funded by: Novartis Pharmaceuticals Corporation
Keywords: Indolent nonHodgkin lymphoma, Cellular therapies
Conflicts of interests pertinent to the abstract
N. H. Fowler
Consultant or advisory role: Roche/Genentech, TG Therapeutics,
Verastem, Bayer, Celgene, Novartis
Research funding: Roche, Celgene, Gilead Sciences, TG Therapeutics,
Novartis, Abbvie, BeiGene
M. Dickinson
Consultant or advisory role: Novartis, BristolMyers Squibb, Gilead
Sciences, Roche, Janssen
Honoraria: Roche, Amgen, MSD, Janssen, BristolMyers Squibb,
Novartis
Research funding: Novartis, Roche, Takeda, Celgene, MSD
Educational grants: Roche
Other remuneration: Speakers' Bureau: Novartis
J. MartinezLopez
Consultant or advisory role: Janssen, Novartis, BMS, Incite, Astellas,
Glaxo
Stock ownership: Altum Sequencing
Research funding: BMS, Roche
Other remuneration: Speakers' Bureau: Janssen, Novartis, BMS,
Incite, Astellas, Glaxo
A. Kolstad
Consultant or advisory role: Nordic Nanovector
Research funding: Merck, Nordic Nanovector
Educational grants: Nordic Nanovector
S. J. Schuster
Consultant or advisory role: Celgene, Nordic Nanovector, Novartis,
Abbvie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene,
Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/
Roche
Honoraria: Novartis, Celgene
Research funding: Novartis, Pharmacyclics, Adaptaive Bio-
technologies, Merck, Genentech/Roche, Celgene, Juno Therapeutics,
Abbvie, Incyte, TG Therapeutics, DTRM
Other remuneration: Patent Combination Therapies of CAR and PD
1 Inhibitors (via University of Pennsylvania with royalties to
Novartis)
M. Dreyling
Consultant or advisory role: Acerta Pharma/AstraZeneca; Bayer/Vi-
tal; Celgene/JAzz; Gilead Sciences; JanssenCilag; Noavrtis; Roche;
Beigene
Research funding: Celgene; JanssenCilag; RochePharma AG; Abbvie
Educational grants: Celgene; JanssenCilag; RochePharma AG
Other remuneration: Bayer Health; Celgene; Gilead Sciences; Jans-
senCilag; RochePharma AG
M. Ghosh
Research funding: Novartis; BMS
H. Harigae
Honoraria: BMS, Novaritis, Chugai, Janssen
Research funding: Astellas
M. José Kersten
Consultant or advisory role: Novartis; Kite a Gilead Company; Mil-
tenyi Biotec; Takeda
Honoraria: Novartis; Kite a Gilead Company; Roche
Educational grants: Novartis; Kite a Gilead Company; Roche; Celgene
E. Bachy
Consultant or advisory role: Roche; Incyte
Honoraria: Roche; Janssen; Celgene; Novartis; Gilead
Research funding: Takeda; Amgen
Other remuneration: Roche; Beigene; Celgene; Abbvie
L. Popplewell
Honoraria: Pfizer; Roche
Educational grants: Novartis
J. C. Chavez
Consultant or advisory role: Kite/Gilead; Novartis; Bayer; Kar-
yopharm Therapeutics; Verastem; Pfizer; Morphosys; TeneoBio; Juno
Therapeutics; Celgene
Research funding: Merck
Other remuneration: Kite/Gilead; Genentech; AstraZeneca; BeiGene
P. J. Ho
Research funding: Abbvie; Celgene; La Jolla Pharma; Novartis; Pi
Square LLC; Takeda
J. Butler
Consultant or advisory role: Novartis
Other remuneration: Novartis
K. Kato
Consultant or advisory role: AbbVie; AstraZeneca; Celgene; Chugai;
Eisai; Janssen; Novartis; Daiichi Sankyo
Honoraria: Takeda; MSD; KyowaKirin; Janssen; Celgene; Ono;
Mundi; DainipponSumitomo; BristolMyersSquibb
Research funding: Chugai; Takeda; KyowaKirin; AbbVie; Novartis;
Eisai; Janssen; Celgene; Ono; Daiichi Sankyo
B. von Tresckow
Honoraria: Amgen; Pfizer; Kite/Gilead; Roche; MSD; Takeda
Research funding: MSD; Takeda; Novartis
Educational grants: MSD; Takeda; Novartis
360
-
SUPPLEMENT ABSTRACTS
A. J. M. Ferreri
Consultant or advisory role: Gilead
Research funding: Gilead; Morphosys; Hutchinson; BMS
J. A. P. Simón
Consultant or advisory role: Novartis; Gilead; Jassen; JAZZ;Hono-
raria: Novartis ; Gilead; Jassen; JAZZ; AMGEN
Other remuneration: Gilead
P. E. M. Patten
Consultant or advisory role: Abbvie; Gilead; Janssen; Novartis; Roche
Honoraria: Abbvie; Astra Zeneca; Gilead; Janssen; Novartis; Roche
Research funding: Gilead
C. Andreadis
Consultant or advisory role: Gilead Sciences; Kite Pharma; Kar-
yopharm Therapeutics; Atara Biotherapeutics; Incyte; TG Therapeu-
tics; Epizyme
Research funding: Novartis; GlaxoSmithKline; Amgen; Jumo Thera-
peutics; Celgene; Merck
Educational grants: Gilead Sciences; Kite Pharma; ROche/Genentech
P. A. Riedell
Honoraria: Kite/Gilead; Celgene/BMS; Takeda; Verastem; Novartis;
Karyopharm Therapeutics; Bayer
Research funding: Kite/Gilead; Celgene/BMS; MorphoSys; Novartis;
Calibr
Other remuneration: Novartis
J. P. McGuirk
Consultant or advisory role: Juno Therapeutics; AlloVir
Honoraria: Kite Pharmaceuticals; Juno Therapeutics; AlloVir
Research funding: Novartis; Fresenius Biotech; Astellas; Bellicum
Pharmaceuticals; Kite Pharmaceuticals; Gamida Cell; Pluristem Ltd;
Juno Therapeutics; AlloVir
Other remuneration: Kite Pharmaceuticals
L. J. Nastoupil
Honoraria: Bayer; Celgene/BMS; Gamida Cell; Gilead/KITE; Janssen;
Novartis; Pfizer; TG Therapeutics; Genentech/Roche
Research funding: Celgene/BMS; Janssen; Karus Therapeutics; LAM
Therapeutics; Merck; Novartis; Pfizer; TG Therapeutics; Genentech/
Roche
T. Teshima
Consultant or advisory role: Merck Sharp & Dohme Corp; Takeda
Pharmaceutical Company Limited; Novartis Pharma K.K.
Honoraria: Merck Sharp & Dohme Corp; Kyowa Kirin Co., Ltd.;
Takeda Pharmaceutical Company Limited; Pfizer Japan Inc.; Bristol
Myers Squibb; TEIJIN PHARMA LIMITED.; Fuji Pharma Co., Ltd.;
NIPPON SHINYAKU CO.,LTD.
Research funding: Kyowa Kirin Co., Ltd.; Novartis Pharma K.
K.; Astellas Pharma Inc.; Chugai Pharmaceutical Co., Ltd.,; Sanofi
K.K
Other remuneration: Kyowa Kirin Co., Ltd.; Novartis Pharma K.K.;
Janssen Pharmaceutical K.K.; Japan Society for the Promotion of
Science KAKENHI (17H04206); The Center of Innovation Program
from Japan Science and Technology Agency
A. Petzer
Consultant or advisory role: Novartis; KiteGilead; Celgene; Roche;
Janssen; Amgen
Honoraria: Novartis; KiteGilead; Celgene; Roche; Janssen; Amgen
A. Viardot
Consultant or advisory role: Amgen; Kite/Gilead; Roche
Honoraria: Pfizer; Roche
Educational grants: Abbvie; BristolMyers Squibb; Janssen; Kite, a
Gilead company; Roche
P. L. Zinzani
Employment or leadership position: Servier; EUSA Pharma
Honoraria: Servier; Takeda; TG Therapeutics; Gilead; Merck; BMS;
Roche; EUSA Pharma; Verastem; Janssen; Kirin Kyowa; DC Thera-
peutics; Abbvie
Other remuneration: Servier; Takeda; TG Therapeutics; Gilead;
Merck; BMS; Roche; EUSA Pharma; Verastem; Janssen; Kirin Kyowa;
DC Therapeutics; Abbvie
R. Malladi
Consultant or advisory role: Novartis
Honoraria: Novartis
J. Zhang
Employment or leadership position: Novartis Pharmaceutical
Corporation
Stock ownership: Novartis Pharmaceutical Corporation
R. Tiwari
Employment or leadership position: Novartis Pharmaceutical
Corporation
Stock ownership: Novartis Pharmaceutical Corporation
V. Bollu
Employment or leadership position: Novartis Pharmaceutical
Corporation
Stock ownership: Novartis Pharmaceutical Corporation
A. Masood
Employment or leadership position: Novartis Pharmaceutical
Corporation
Stock ownership: Novartis Pharmaceutical Corporation
C. Thieblemont
Honoraria: Celgene; Abbvie; Bayer; Janssen; Roche; Incyte; Novartis;
Gilead Sciences
Research funding: Roche
Educational grants: Roche; JanssenCilag; Kite/Gilead; Novartis
SUPPLEMENT ABSTRACTS
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361
267 |SAFETY AND EFFICACY OF TISAGENLECLEUCEL PLUS
PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY
DIFFUSE LARGE BCELL LYMPHOMA: UPDATED ANALYSIS OF
THE PHASE 1B PORTIA STUDY
U. Jaeger
1
, N. Worel
2
, J. P. McGuirk
3
, P. A. Riedell
4
, I. Fleury
5
, P.
Borchmann
6
, Y. Du
7
, X. Han
8
, M. MartinezPrieto
9
, E. K. Waller
10
1
Medical University of Vienna, Vienna, Austria,
2
Medical University of
Vienna, Vienna, Austria,
3
Division of Hematologic Malignancies and
Cellular Therapeutics, University of Kansas Medical Center, Kansas
City, USA,
4
University of Chicago, Chicago, USA,
5
Maisonneuve
Rosemont Hospital, University of Montreal, Montreal, Canada,
6
Uni-
versity Hospital Cologne, Cologne, Germany,
7
Novartis Pharma AG,
Shanghai, China,
8
Novartis Pharmaceuticals Corporation, East Hanover,
USA,
9
Novartis Oncology, Novartis Pharmaceuticals Corporation, East
Hanover, USA,
10
Emory University Winship Cancer Institute, Atlanta,
Georgia, USA
Background: Tisagenlecleucel (Tisacel) showed durable responses
and manageable safety in patients (pts) with relapsed/refractory
diffuse large Bcell lymphoma (r/r DLBCL) in the JULIET trial. High
baseline programmed cell death 1 (PD1) expression associated with
higher probability of no response (Schuster et al. NEJM 2019). Here
we report an updated analysis of PORTIA, a phase 1b, multicenter,
openlabel study of tisacel plus pembrolizumab (pembro) in pts with
r/r DLBCL (NCT03630159).
Methods: Eligible pts (18 y) had r/r DLBCL after 2 lines of therapy
and relapsed after or were not candidates for autologous stem cell
transplant (autoSCT). Pts received a single tisacel infusion on Day 1
and were enrolled in 1 of 3 cohorts that initiated pembro (200 mg q 21
days, up to 6 doses) on either Days +15, +8, or –1. Primary endpoints
were incidence of doselimiting toxicities (DLTs) and overall response
rate (ORR; complete response [CR] and partial response [PR]). Sec-
ondary endpoints included duration of response, progressionfree
survival, overall survival, safety, and cellular kinetics.
Results: As of November 9, 2020, 15 pts were enrolled and 12
received tisacel (n =4 pts for each Days +15, +8, and –1 cohorts;
median followup, 4 mo). At study entry, the median age among
treated pts was 62 y (range, 3579), 100% had an International
Prognostic Index score 2, 67% had 3 prior lines of therapy, 58%
had stage IV disease, 58% had lactate dehydrogenase >ULN, and
42% had prior autoSCT. All 12 pts had 1 AE. Grade 3 AEs
suspected to be related to tisacel and/or pembro were neutropenia
(n =4); neutrophil count decreased (n =3); febrile neutropenia,
lymphocyte count decreased, malnutrition (each n =2); anemia,
leukopenia, diarrhea, white blood count decreased, liver function
tests increased, thrombocytopenia, hepatitis, and cytokine release
syndrome (CRS; each n =1). No neurotoxicity or DLTs were
observed. Among the Day +15, +8, and –1 cohorts (each n =4), the
ORR was 50% (2/4; CR n =0, PR n =2), 25% (1/4; CR n =1, PR n =
0), and 25% (1/4; CR n =1, PR n =0; longer followup is needed for n
=2 pts), respectively. Tisacel exposure and peak expansion were
consistent with JULIET, with a trend toward delayed expansion in the
Day –1 cohort (n =4). There was no sign of secondary expansion
following pembro administration regardless of the number of doses.
Compared with JULIET, lower CRS severity and frequency and lower
cytokine profiles were observed for all 3 cohorts.
Conclusions: The combination of tisacel plus pembro was feasible
and showed manageable safety. The lack of improved efficacy in
PORTIA with the addition of pembro compared with tisacel alone
may be related to more pts with 3 prior lines of therapy (67% vs
51%, respectively), and/or pts with more advanced disease in
PORTIA. Additional studies with larger patient cohorts are needed to
determine the value of adding PD1 inhibitors to CART cell therapy
in pts with r/r DLBCL.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: Novartis Pharmaceuticals Corporation
Keywords: Aggressive Bcell nonHodgkin lymphoma, NonHodgkin
(Pediatric, Adolescent, and Young Adult)
Conflicts of interests pertinent to the abstract
U. Jaeger
Consultant or advisory role: Novartis, Celgene/BMS, Miltenyi Biotec,
CDRLife
Honoraria: Abbvie, Novartis, Gilead, Celgene/BMS, Karyopharm
Therapeutcis, Miltenyi Biotec, Roche
Research funding: To InstitutionNovartis, Gilead, Celgene/BMS,
CDRLife, Roche
N. Worel
Consultant or advisory role: Novartis, Celgene/BMS
Research funding: To InstitutionSanofi
Educational grants: Therakos/Mallinkrodt, Celgene/BMS
Other remuneration: Speaker BureauSanofi, Novartis, Kite/Gilead,
Therakos/Mallinkrodt
J. P. McGuirk
Consultant or advisory role: Kite, Juno, Allovir, Magenta Therapeu-
tics, EcoR1 Cap
Honoraria: Kite, Allovir, Juno, Magenta Therapeutics
Research funding: To InstitutionNovartis, Fresenius Biotech, Astel-
las, Bellicum, Gamida Cell, Pluristem Therapeutics, Kite, Allovir
Educational grants: Kite
Other remuneration: Speakers' BureauKite
P. A. Riedell
Honoraria: Kite, Celgene/BMS, Takeda Verastem, Novartis, Kar-
yopharm Therapeutics, Bayer
Research funding: To InstitutionKite. Celgene/BMS, MorphoSys,
Novartis, Calibr
Other remuneration: Novartis
I. Fleury
Consultant or advisory role: Abbvie, AstraZeneca, Gilead, Janssen,
Novartis, Roche, Seattle Genetics
Honoraria: Abbvie, Gilead, Janssen, Novartis, Roche, Seattle Genetics
362
-
SUPPLEMENT ABSTRACTS
Y. Du
Employment or leadership position: Novartis Pharmaceuticals
Corporation
X. Han
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
M. MartinezPrieto
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
Honoraria: Novartis Pharmaceuticals Corporation
E. K. Waller
Employment or leadership position: Cambium Medical Technologies
Consultant or advisory role: Novartis, Verastem, Pharmacyclics,
Karyopharm, Partners Healthcare, Kite,
Stock ownership: Cambium Medical Technologies, Cerus, Chimerix
Honoraria: Novartis, Verastem, Pharmacyclics, Karyopharm, Partners
Healthcare, Kite,
Research funding: Novartis, Amgen, Juno, Verastem, Partners
Healthcare
Educational grants: Pharmacyclics
Other remuneration: Royalties from patent on platelet lysate that
has been licensed to Cambuim Medical Technologies
268 |RELAPSE CHARACTERIZATION IN DIFFUSE LARGE B
CELL LYMPHOMA PATIENTS UNDERGOING COMMERCIAL CAR
T CELL THERAPY: EXPERIENCE FROM A SINGLE CENTRE
M. BastosOreiro
1
, R. Bailén
1
, P. Silva
2
, S. Monsalvo
2
, A. Pérez
Corral
2
, D. Carbonell
2
, F. Díaz Crespo
3
, I. GómezFernández
4
, G.
Oarbeascoa
2
, N. Dorado
2
, C. Muñoz
2
, S. Sabell
2
, J. Menarguez
3
, C.
MartínezLaperche
2
, I. Buño
2
, J. Anguita Velasco
2
, J. L. DíezMartín
2
,
M. Kwon
2
1
Hospital Universitario Gregorio Marañón, *equal contribution,
Hematology, Madrid, Spain,
2
Hospital Universitario Gregorio Marañón,
Hematology, Madrid, Spain,
3
Hospital Universitario Gregorio Marañón,
Pathology, Madrid, Spain,
4
Hospital Universitario Gregorio Marañón,
Medicina Nuclear, Madrid, Spain
Background: CART cell therapy is approved for the treatment of
adults with relapsed or refractory (R/R) diffuse large Bcell lym-
phoma (DLBCL). However, 4060% of patients relapse after therapy
and characterization of relapse has been poorly reported.
Aims: To describe relapse characteristics in biopsy samples in pa-
tients with DLBCL receiving CART cell therapy in our center.
Methods: All consecutive patients diagnosed with R/R DLBCL who
were infused with commercial CART cells from June 2019 to
December 2020 were included.
CART cell expansion in PB was monitored by multiparameter
flow cytometry (FC) through detection of labeled CD19 in T cells
(Human CD19 Protein®). PETCT scanner evaluation was performed
on days +30, +90 and +180. In cases where PETCT detected pro-
gression or indeterminate response, coreneedle biopsy of the
accessible lesions was performed. Study of biopsy included: histo-
logical analysis; FC immune phenotyping including CART cell pres-
ence and detection of exhausted CD3+populations (LAG3, TIM3,
PD1). DNA was purified from biopsy using GeneRead DNA FFPE Kit
(Qiagen). Mutations of CD19 (exon25) were analyzed by Sanger
sequencing.
Results: 30 patients with R/R lymphoma were treated: 21 with axi
cel 9 with tisacel. Median age at infusion was 57 years (r: 2279);
16 (53%) were female. Median follow upwas 9.5 months (r: 318).
PFS at 6 months was 42% and OS 72%. CART cell expansion in PB
was detected in 29 patients (97%). Complete and overall response
TABLE 1Characteristics of the population at replapse
SUPPLEMENT ABSTRACTS
-
363
rate at day 30 (CR and ORR) were 39% and 75%, respectively (28
evaluable patients), and 41% and 55% at day 100, respectively (27
evaluable patients). At day 180, 10 out of 14 evaluable patients
(38.5%) showed CR. A total of 15 patients experienced relapse or
progression. Biopsy of the accessible lesions was performed in 10
(66%) (Table 1). Relapsed was confirmed in all cases except in one in
whom sample was insufficient. Three patients who were CD19+by
IHQ on the preinfusion biopsy showed CD19at relapse. CART cell
in PB at relapse was detected in all except one patient that did not
expand CART after 2 infusions and 60% of patients presented CAR
T in the biopsy. TME (tumor microenvironment) TCD3+lymphocytes
were >20% in 80% of the cases and no patient had <5%. In tumor
sample, FC failed to identify cellularity in 37% of patients; in the rest
of samples, percentage of exhausted TCD3 presented an average of
80% (range 6484). CD19 study revealed mutation in one patient (p.
V279L) who presented a CD19+relapse.
Conclusions: In our series of relapsed lymphomas after CART anti
CD19 treatment, CART cell was present in all patients in PB but
only 60% in tissue. CD19 loss and mutations in DNA are possible
relapse mechanisms. Exhausted TCD3 lymphocytes were abundant in
TME, which would support its relevant role preventing a good
function of the carts in situ. More complex biopsies analyses are
necessary to better understand relapse mechanisms.
Keywords: Tumor Biology and Heterogeneity, Aggressive Bcell non
Hodgkin lymphoma, Cellular therapies
No conflicts of interests pertinent to the abstract.
269 |A SINGLEARM, OPENLABEL, PILOT TRIAL OF
AUTOLOGOUS CD7CART CELLS FOR CD7 POSITIVE RELAPSED
AND REFRACTORY TLYMPHOBLASTIC LEUKEMIA/LYMPHOMA
M. Zhang
1
, M. Zhang
1
, X. Fu
1
, H. Meng
2
, D. Chen
2
, M. Wang
2
, L.
Zhang
1
, L. Li
1
, X. Li
1
, X. Wang
1
, Z. Sun
1
, H. Yu
1
, Z. Li
1
, F. Nan
1
, Y.
Chang
1
, Z. Zhou
1
, J. Yan
1
, J. Li
1
, Y. Wang
3
, F. You
2
, Y. Wang
2
, S.
Xiang
2
, Y. Chen
3
, G. Pan
3
, H. Xu
3
, B. Zhang
2
, L. Yang
2
1
The First Affiliated Hospital of Zhengzhou University, Department of
Oncology, Zhengzhou, China,
2
PersonGen BioTherapeutics (Suzhou) Co.,
Ltd., PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China,
3
PersonGenAnke Cellular Therapeutics Co., Ltd, PersonGenAnke Cellular
Therapeutics Co., Ltd, Suzhou, China
Introduction: T lymphoblastic leukemia/lymphoma (TALL/LBL) is
highly aggressive. Although intensive chemotherapies such as ALL
type regimens are commonly used, about half patients eventually
relapse and die of TALL/LBL. Chimeric antigen receptor (CAR) T
cells have given rise to breakthroughs in treating B cell hematological
malignancies. However, there are few clinical studies of CART on T
cell malignant tumors. CD7, overexpressed in up to 100% of
relapsed/refractory TALL/LBL, is an attractive therapeutic target for
Tlymphoblastic leukemia/lymphoma (TALL/LBL). Now, a nanobody
derived CD7CART with a highly optimized structure and a clinically
feasible strategy to overcome CART cell fratricide and exclude
abnormal T cell contamination have been developed. Preclinical
studies have demonstrated CD7 CAR T cells produced robust cyto-
toxicity against malignant Tcell lines and primary tumors and were
protective in a mouse xenograft model of TALL.
Method: This is a singlearm, open label, safety and efficacy pilot
study (NCT04004637). Study participants will receive Flu/Cy pre
treatment before CART infusion. CD7 CART was then adminis-
tered at a single dose of 1.0 10
6
(N =5) or 1.5 10
6
(N =1; Pt#1)
or 2 10
6
(N =3; Pt#7, 8, 9) CART cells/kg. Adverse events were
categorized by NCICTCAE V5.0. Tumor response were assessed
based on the 2014 Lugano Evaluation Criteria for Lymphoma and
2016 Chinese Guideline for Diagnosis and Treatment of Acute
Lymphoblastic Leukemia.
Results: Up to now, a total of 9 patients including 6 r/r TALL/LBL
and 3 r/r ETPALL/LBL (case 4, 5, 6) were assigned to receive CD7
CART cell and completed the efficacy assessment. Overall response
rate at 1 month was 100%. In patients followed up for 3 months,
complete remission (CR) rate at 3 month was 71.4%. Case 16 was
administered at 1.010
6
CART/Kg except for case 1 (1.0 10
6
CART/Kg). Bone marrow (BM) tumor burden of case 1 decreased
from 70.03% to 19.51% and case 1 has an OS more than 15 months.
Case 2 died due to abdominal infection at 3 month although he was
still in MRDstatus then. Case 3 had sustained MRDfor 7 months
but appeared MRD+in BM at 8 month, so second CD7 CART
infusion had been performed and patient achieved CR at 14th day.
Case 4 has been achieving CR more than 9 months and is still in
remission. Case 5 and 6 had a DOR (Duration of response) of about 4
and 3 months respectively. In case 16, despite case12 appeared
grade 2 CRS, all other cases only had grade 1. Therefore, in order to
further explore the best effective dose, case 79 had received dose of
2.0 10
6
CART/Kg. Case 89 are still in complete remission.
Unfortunately, case 6 relapsed at 6 month due to CD7 negative
blasts. The absence of CD7 on the cell surface enables the tumor to
evade CAR T cellmediated recognition and clearance, despite
continued persistence of CART cells.
Conclusions: Autologous CD7 CART is a novel immunotherapy for
r/r TALL/LBL and exhibited encouraging clinical efficacy and safety
in treating r/r TALL/LBL and ETPALL/LBL.
The research was funded by: Comprehensive and Digital Technology
Demonstration Platform for Clinical Evaluation of New Drugs for
Major Diseases, National Key Research and Development Project,
(2020ZX09201009)
Keywords: Aggressive Tcell nonHodgkin lymphoma, Cellular ther-
apies, Immunotherapy
Conflicts of interests pertinent to the abstract
H. Meng
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
364
-
SUPPLEMENT ABSTRACTS
D. Chen
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
M. Wang
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
Y. Wang
Employment or leadership position: PersonGenAnke Cellular Ther-
apeutics Co., Ltd.
F. You
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
Y. Wang
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
S. Xiang
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
Y. Chen
Employment or leadership position: PersonGenAnke Cellular Ther-
apeutics Co., Ltd.
G. Pan
Employment or leadership position: PersonGenAnke Cellular Ther-
apeutics Co., Ltd.
H. Xu
Employment or leadership position: PersonGenAnke Cellular Ther-
apeutics Co., Ltd.
B. Zhang
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
L. Yang
Employment or leadership position: PersonGen BioTherapeutics
(Suzhou) Co., Ltd.
270 |PATIENTS WITH OUT OF SPECIFICATION
TISAGENLECLEUCEL CAN BE SALVAGED WITH A POINTOF
CARE CAR TCELLS: AN OBSERVATIONAL INTENTIONTOTREAT
SINGLECENTER ANALYSIS
S. Fried
1
, R. Shouval
2
, N. VardaBloom
3
, M. Besser
4
, R. Yerushalmi
1
,
N. ShemTov
1
, I. Danylesko
1
, E. Jacoby
5
, S. Teihman
3
, A. Shimoni
1
, A.
Nagler
1
, A. Avigdor
1
1
Chaim Sheba Medical Center, Division of Hematology and Bone Marrow
Transplantation, Tel Hashomer, Israel,
2
Memorial Sloan Kettering Cancer
Center, Adult BMT Service, New York, USA,
3
Chaim Sheba Medical
Center, Hematology Laboratory, Tel Hashomer, Israel,
4
Chaim Sheba
Medical Center, Ella Lemelbaum Institute for Immuno Oncology, Tel
Hashomer, Israel,
5
Chaim Sheba Medical Center, Department of Pediatric
HematologyOncology, Safra Children's Hospital, Tel Hashomer, Israel
Introduction: Tisagenlecleucel (Tisacel) is an antiCD19 chimeric
antigen receptor (CAR) Tcell therapy approved for patients (pts)
with relapsed/refractory diffuse large Bcell lymphoma (DLBCL).
Results from the JULIET trial showed best overall response of 52%
per protocol and 34% in an intentiontotreat (ITT) analysis. Out-
comes of pts with out of commercial specification (OOS) products are
not well established. Availability of pointofcare antiCD19/CD28
costimulatory domain academic CAR Tcells in our center allows us
SUPPLEMENT ABSTRACTS
-
365
to provide rapid salvage in cases of commercial CAR Tcell produc-
tion failure.
Methods: Data of pts who underwent leukapheresis for Tisacel in a
single center were collected. Survival was calculated from
leukapheresis.
Results: Peripheral blood cells were collected from 37 pts with
DLBCL between 05/2019 and 02/2020. Median age at leukapheresis
was 63 (range 2879) years. Median number of prior therapies was 2
(range 26). Cells from 78% of the pts were collected in progressive
disease. Bridging therapy was given to 87% of pts. Median time from
leukapheresis to cell infusion was 1.6 (range 1.32.2) months. During
this time, disease progression was marked in 45% of the pts. Tisacel
CAR Tcells were infused in 29 (78%) of the pts. Median followup is
14.7 months.
In 9 (24%) pts, manufactured Tisacel did not meet specifications
for commercial release. Causes for OOS were production termination
(3 [33%]), low CAR viability (<70%; [33%]) and low CAR dose (<0.6
10
8
; [33%]). Among pts with OOS products, 3/9 (33%) received Tisa
cel despite not meeting production standards; 2/9 (22%) did not
receive Tisacel due to disease progression; and 4/9 (44%) were
salvaged with pointofcare CAR Tcells, at a median of 35 (range 16
92) days following OOS notification. Three of these four pts achieved
a complete response (CR) (Figure 1A). In a univariate analysis, risk
factors for OOS were 4 prior therapies (p =0.04) and exposure to
bendamustine (p =0.04). Bone marrow transplantation and age 65
were not significant risk factors.
Overall response at day28 postCAR T was 46% (CR 24%) and
35% (CR 24%) per protocol (i.e., including only pts received Tisacel)
and in ITT (i.e., including all pts underwent leukapheresis), respec-
tively. One year overall survival (OS) was 65% (95% CI 5085%) per
protocol and 56% (95% CI 4275%) in ITT (Figure 1B). In a multi-
variable ITT Cox regression, factors associated with a shorter OS
were ECOG 2 (HR 6.5; 95% CI 1.922.5) and primary refractory
disease (HR 3.3; 95% CI 1.29.1). OOS was not a significant risk factor
for a shorter OS (p =0.07), nor age, disease stage, and LDH at
leukapheresis.
Conclusion: Our data show relatively high rates of OOS products
following leukapheresis for Tisacel. We highlight the ability to
rapidly produce pointofcare CAR Tcells, facilitating immune
effector cell salvage of pts who experienced production failure of
the commercial product.
EA previously submitted to EHA 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Cellular
therapies
No conflicts of interests pertinent to the abstract.
271 |EXTRANODAL DISEASE IS ASSOCIATED WITH SHORTER
PROGRESSIONFREE SURVIVAL AFTER CD19CAR TCELL
THERAPY FOR RELAPSED/REFRACTORY DIFFUSE LARGE BCELL
LYMPHOMA
V. Bücklein
1
, V. Blumenberg
1
, J. Ackermann
1
, L. Frölich
1
, M.
Winkelmann
2
, C. Schmidt
1
, K. Rejeski
1
, M. Ruzicka
1
, N. Müller
1
, L. von
Baumgarten
3
, F. Schöberl
4
, M. Hildebrandt
5
, A. Humpe
5
, W. Kunz
2
, E.
Hoster
6
, M. von Bergwelt
1
, M. Subklewe
1
1
University Hospital, LMU Munich, Department of Medicine III, Munich,
Germany,
2
University Hospital, LMU Munich, Department of Radiology,
Munich, Germany,
3
University Hospital, LMU Munich, Department of
Neurosurgery, Munich, Germany,
4
University Hospital, LMU Munich,
Department of Neurology, Munich, Germany,
5
University Hospital, LMU
Munich, Department of Transfusion Medicine, Munich, Germany,
6
LMU
FIGURE 1A Patients‘ outcome after Tisacel OOS
FIGURE 1B Overall survival in an intentiontotreat analysis
366
-
SUPPLEMENT ABSTRACTS
Munich, Institute for Medical Information Processing, Biometry, and
Epidemiology, Munich, Germany
Introduction: CD19 CAR T cells induce complete remissions in 40%
of heavily pretreated patients with relapsed/refractory (r/r) diffuse
large Bcell lymphoma (DLBCL). However, a significant proportion of
patients progress early after therapy. Thus, to prospectively identify
patients most suitable for currently available commercial CAR Tcell
products, we assessed the predictive value of clinical and laboratory
parameters for PFS in r/r DLBCL patients treated with Axicabtagene
Ciloleucel or Tisagenlecleucel at our institution.
Methods: Patient, disease, and treatment characteristics of r/r
DLBCL patients treated with CD19CAR T cells were retrospectively
assessed. Predefined patient and lymphoma characteristics known
to confer adverse outcomes in DLBCL were evaluated for their as-
sociation with PFS by univariable logrank tests, as well as multi-
variable stepwise Cox regression analyses. Characteristics
encompassed age, refractoriness to firstline therapy, no. of prior
therapy lines, tumor volume, presence of bulky disease, presence of
extranodal disease (END), Ann Arbor stage, IPI, LDH, and ECOG, all
assessed at time of lymphodepletion.
Results: As of November 2020, 35 patients have been transfused.
Median age was 60 years (range 1982). ECOG was 01 in 23, and 2
3 in twelve patients at CAR Tcell transfusion. Only 3 of the 35
transfused patients (9%) would have met the inclusion criteria of the
pivotal clinical trials at all eligibility assessment timepoints (enrol-
ment, apheresis, and time of lymphodepletion).
CRS occurred in 32/35 patients (80% CRS °12, 11% °3). 16
patients (46%) experienced ICANS (29% °12, 14% °34, and 3% °5).
Response assessment after three months was available for 34/35
patients. Objective response rate was 53%, with complete remission
in 15 (44%) and partial remission in three patients (9%).
In univariable analyses, apart from primary refractory disease
(p =0.79), all preselected characteristics were suggestive to be
associated with shorter PFS (p =0.0020.061). We therefore
included these variables (p <0.1) in multivariable Cox regression
analyses. In the resulting model, presence of END was associated
with inferior PFS (Hazard ratio [HR] 11.3, p =0.02), adjusted for
prior therapy lines (HR 1.3, p =0.06) and ECOG >1 (HR 2.3, p =
0.12). Other variables did not improve the prognostic validity of the
model.
Conclusions: We provide realworld evidence that CD19CAR T cells
induce remissions in a substantial proportion of r/r DLBCL patients,
despite very frequent noneligibility for pivotal clinical trials in our
patient cohort. Extranodal disease at transfusion was associated with
significantly shorter PFS both in uniand multivariable analyses. To
address ENDassociated resistance mechanisms, we have set up a
comprehensive translational research program with specific focus on
the nodal vs. extranodal lymphoma microenvironment.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Cellular
therapies
Conflicts of interests pertinent to the abstract
V. Bücklein
Consultant or advisory role: Pfizer, Amgen, Kite Gilead
Research funding: Novartis, Celgene, Kite Gilead
272 |COMPARATIVE EFFICACY OF TISAGENLECLEUCEL (TISA
CEL) AND LISOCABTAGENE MARALEUCEL (LISOCEL) IN
RELAPSED/REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA
(R/R DLBCL)
R. T. Maziarz
1
, J. Zhang
2
, H. Yang
3
, A. Agarwal
4
, W. Tang
5
, M.
MartinezPrieto
6
, V. Bollu
7
, D. Kuzan
8
, S. J. Schuster
9
, M. J. Kersten
10
1
Knight Cancer Institute, Oregon Health and Science University, Portland,
Oregon, USA,
2
Novartis Oncology, Novartis Pharmaceuticals Corporation,
East Hanover, USA,
3
Analysis Group, Inc., Boston, USA,
4
Novartis
Oncology, Novartis Pharmaceuticals Corporation, East Hanover, USA,
5
Analysis Group, Inc., Boston, USA,
6
Novartis Oncology, Novartis
Pharmaceuticals Corporation, East Hanover, USA,
7
Novartis US Oncology,
Novartis Pharmaceuticals Corporation, East Hanover, USA,
8
Novartis
Oncology, Novartis Pharmaceuticals Corporation, East Hanover, USA,
9
Lymphoma Program, Abramson Cancer Center of the University of
Pennsylvania, Philadelphia, USA,
10
Academic Medical Center, University
of Amsterdam, Amsterdam, Netherlands
Introduction: Chimeric antigen receptor Tcell therapies tisacel and
lisocel are effective treatments for r/r DLBCL (Schuster 2019,
Abramson 2020). This study compared efficacy outcomes of tisacel
and lisocel in r/r DLBCL using matchingadjusted indirect compari-
son (MAIC).
Methods: Individual patientlevel data (IPD) from JULIET (tisacel;
NCT02445248; 02/2020 datacut) were weighted to match the pa-
tient population in TRANSCEND (lisocel; NCT02631044; 08/2019
datacut). Baseline prognostic factors available in both trials were
adjusted for age, sex, histology, ECOG performance status [ECOG
PS], left ventricular ejection fraction, radiologic sum of product di-
ameters, lactate dehydrogenase, prior stem cell transplantation
[SCT], use of bridging therapy, and number of and refractoriness to
prior therapies, in the MAIC. Overall survival (OS), progressionfree
survival (PFS), complete response (CR) rate, and overall response
(OR) rate were compared. Primary analyses compared infused pa-
tients in JULIET (N =106, excluding 8 without lymphodepleting
chemotherapy [LDC] and 1 large cell neuroendocrine carcinoma)
with efficacyevaluable set in TRANSCEND (N =256, infused pa-
tients). A scenario analysis compared JULIET infused to TRAN-
SCEND primary analysis set (PAS) (N =133, dose level 2, excluding
those with ECOG PS 2, prior allogeneic SCT, primary mediastinal B
cell lymphoma, follicular lymphoma [FL] 3B, or transformation from
indolent lymphoma besides FL). Sensitivity analyses included JULIET
patients with only fludarabinebased LDC or only adjusted signifi-
cantly different baseline prognostic factors. Safety outcomes were
not compared because adverse event management has evolved and
differed between the two trials; MAIC is unable to adjust for such
differences.
SUPPLEMENT ABSTRACTS
-
367
Results: After adjusting for differences in baseline characteristics,
OS, PFS, and CR were comparable between tisacel infused patients
and the lisocel efficacyevaluable set (Table). The results were
consistent across all scenario and sensitivity analyses. OR rate
trended higher in the TRANSCEND efficacyevaluable set (72.7% vs.
62.9%, p =0.07) and was higher in TRANSCEND PAS than in the
respectively matched JULIET infused set (74.4% vs. 60.9%, p <0.05).
Conclusions: The MAIC results indicate there is no evidence sug-
gesting differences in OS, PFS and CR between tisacel and lisocel in
r/r DLBCL. Analyses using IPD from both trials and/or realworld
evidence are warranted to confirm these findings.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: Novartis Pharmaceuticals Corporation
Keywords: Aggressive Bcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
R. T. Maziarz
Employment or leadership position: Knight Cancer Institute, Oregon
Health and Science University
Consultant or advisory role: Novartis, Incyte, Kite Pharmaceuticals,
BristolMyers Squibb, Intellia, Artiva Therapeutics
Honoraria: Novartis, Omeros, PACT Pharmaceuticals
Educational grants: Novartis, Incyte, Kite Pharma
J. Zhang
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
H. Yang
Employment or leadership position: Analysis Group
A. Agarwal
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
W. Tang
Employment or leadership position: Analysis Group
M. MartinezPrieto
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
Honoraria: Novartis Pharmaceuticals Corporation
V. Bollu
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
D. Kuzan
Employment or leadership position: Novartis Pharmaceuticals
Corporation
Stock ownership: Novartis Pharmaceuticals Corporation
S. J. Schuster
Employment or leadership position: University of Pennsylvania
Consultant or advisory role: Celgene, Nordic Nanovector, Novartis,
Abbvie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene,
Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/
Roche
Research funding: To InstitutionNovartis, Pharmacyclics, Adaptive
Biotechnologies, Merck, Genentech/Roche, Celgene, Juno Thera-
peutics, Abbvie, Incyte, TG Therapeutics, DTRM
Other remuneration: Patent Combination Therapies of CAR and PD
1 Inhibitors (via University of Pennsylvania with royalties to
Novartis)
M. J. Kersten
Employment or leadership position: University of Amsterdam
Consultant or advisory role: Novartis, Kite, Miltenyi Biotech, Takeda
Honoraria: Novartis, Kite, Roche
Research funding: To InstitutionKite
Educational grants: Novartis, Kite, Roche, Celgene
273 |OUTREACH: PRELIMINARY SAFETY & EFFICACY
RESULTS FROM A PHASE 2 STUDY OF LISOCABTAGENE
MARALEUCEL (LISOCEL) IN THE NONUNIVERSITY SETTING
J. E. Godwin
1
, B. Mattar
2
, M. Maris
3
, C. Bachier
4
, D. A. Stevens
5
, D.
Hoda
6
, J. C. Varela
7
, M. Cherry
8
, S. Fanning
9
, J. Essell
10
, H. Yimer
11
, J.
Courtright
12
, J. Sharman
13
, N. S. Trede
14
, M. Youssef
15
, J. Lymp
16
, P.
Shaughnessy
17
1
Providence Cancer Center, Earle A. Chiles Research Institute, Oncology
Hematology Clinic, Portland, Oregon, USA,
2
Cancer Center of Kansas,
Internal Medicine, Wichita, Kansas, USA,
3
Colorado Blood and Cancer
Institute and Sarah Cannon Research Institute, Hematology/Oncology,
Denver, Colorado, USA,
4
Sarah Cannon Center for Blood Cancer,
Hematology, Nashville, Tennessee, USA,
5
Norton Healthcare, Medical
Oncology, Louisville, Kentucky, USA,
6
Intermountain Healthcare, Loveland
Clinic for Blood Cancer Therapy, Salt Lake City, Utah, USA,
7
Advent
Health , Blood and Marrow Transplant Program, Orlando, Florida, USA,
8
Atlantic Health System, Carol Simon Cancer Center, Morristown, New
Jersey, USA,
9
Prisma Health, Hematology, Greenville, South Carolina, USA,
10
Oncology Hematology Care, Medical Oncology, Hematology, Blood and
TABLE: MAIC of Tisacel Infused vs. Lisocel Efficacyevaluable Set
Tisacel vs. lisocel (95% CI); pvalue
OS, hazard ratio (HR) 1.12 (0.62, 2.05); p =0.71;
1year OS rate: 55.1% vs 57.9%
PFS, HR 1.16 (0.64, 2.09); p =0.63;
1year PFS rate: 47.4% vs 44.1%
CR, rate difference 5.4% (15.5%, 4.7%); p =0.29
OR, rate difference 9.7% (20.0%, 0.6%); p =0.07
368
-
SUPPLEMENT ABSTRACTS
Marrow Transplantation, Cincinnati, Ohio, USA,
11
Texas OncologyTyler,
Hematology, Medical Oncology, Tyler, Texas, USA,
12
Texas Oncology,
Medical City Dallas, Dallas, Texas, USA,
13
Willamette Valley Cancer
Institute, Blood Cancers, General Oncology, Eugene, Oregon, USA,
14
Bristol Myers Squibb, Clinical Development, Seattle, Washington, USA,
15
Bristol Myers Squibb, Global Drug Development, Princeton, New Jersey,
USA,
16
Bristol Myers Squibb, Cell Therapy Biostatistics, Seattle, Wash-
ington, USA,
17
Sarah Cannon Transplant and Cellular Therapy Program,
Methodist Hospital, San Antonio, Texas, USA
Introduction: Concerns about adverse event management related to
chimeric antigen receptor (CAR) T cell therapy have resulted in
administration of this therapy largely in an inpatient setting. Infusion
and monitoring of patients (pts) who receive CAR T cell therapy at
nonuniversity medical centers (NMCs) and in outpatient settings
have not been studied specifically. This study evaluated the safety
and efficacy of lisocel in pts with relapsed/refractory (R/R) large B
cell lymphoma (LBCL) across inpatient and outpatient settings at
NMCs in OUTREACH (NCT03744676).
Methods: This openlabel, multicenter, phase 2 study enrolled adult
pts with R/R LBCL at NMCs, including centers naïve to CAR T cell
therapy. Eligible pts had R/R positron emission tomographypositive
disease after 2 lines of prior systemic therapy, ECOG PS 1, and
adequate organ function. Prior autologous HSCT was permitted.
After leukapheresis and lymphodepleting chemotherapy, pts received
sequential infusions of equal target doses of CD8
+
and CD4
+
cells at
a total target dose of 100 10
6
CAR
+
T cells. The primary endpoint
was incidence of grade 3 cytokine release syndrome (CRS) graded
per 2014 Lee criteria, neurological events (NEs), prolonged cytope-
nias (Day 29 grade 3 lab values), and infections. Secondary end-
points were safety and overall response rate (ORR). All study sites
had a multidisciplinary CAR T cell therapy team and standard oper-
ating procedures (SOPs) for toxicity monitoring/management of pts
treated and/or monitored as outpatients.
Results: At data cutoff, 46 pts (inpatients, n =16; outpatients, n =30)
were treated with lisocel. Median age was 63 (range, 3483) years,
63% had diffuse LBCL not otherwise specified, and 91% were re-
fractory to last therapy. Inpatients and outpatients had similar de-
mographics and baseline disease characteristics. Safety data were
similar across the inpatient and outpatient groups (Table). Overall,
the most common treatmentemergent adverse events were neu-
tropenia (32; 70%), leukopenia (22; 48%), and anemia (18; 39%). Early
(study Day 4) and overall hospitalization was reported in 27% and
63% of outpatients, respectively; median time to hospitalization was
5 (2–61) days and median length of stay was 6 (1–28) days. For
efficacyevaluable pts (n =44), ORR was 75% for inpatients and 79%
for outpatients; complete response rates were 50% and 61%,
respectively.
Conclusions: Lisocel was successfully administered to pts with R/R
LBCL in the outpatient setting and pts were monitored for CAR T cell
therapy–related toxicities by multidisciplinary teams using SOPs.
Incidences of severe CRS and NEs and tocilizumab and/or cortico-
steroid use were similar in inpatients and outpatients. Data were
consistent with pivotal study observations (Abramson JS, et al. Lan-
cet. 2020;396:839852). Updated data with longer followup will be
presented.
EA previously submitted to EBMT, ASCO and EHA 2021.
The research was funded by: This study was funded by Juno
Therapeutics, a BristolMyers Squibb Company. All authors
contributed to and approved the presentation; writing and editorial
assistance were provided by Amy Agbonbhase, PhD, of The
Lockwood Group (Stamford, CT, USA), funded by Bristol Myers
Squibb.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Cellular ther-
apies, OngoingTrials
Conflicts of interests pertinent to the abstract
TABLE: Adverse events of interest
SUPPLEMENT ABSTRACTS
-
369
B. Mattar
Employment or leadership position: Cancer Center of Kansas
Consultant or advisory role: BMS, GSK
C. Bachier
Consultant or advisory role: Juno/BMS, CRISPR, Kadmon, Autolus,
Mana Therapeutics
D. Hoda
Consultant or advisory role: Amgen
J. C. Varela
Consultant or advisory role: Nexlmmune
Stock ownership: Nexlmmune
Honoraria: Nexlmmune, Kite, Omeros
Other remuneration: Speakers Bureau: Kite
S. Fanning
Consultant or advisory role: TG Pharma, Abbvie
Other remuneration: Speakers Bureau: Takeda, BMS, Sanofi
J. Essell
Other remuneration: Speakers Bureau: Kite, BMS
H. Yimer
Other remuneration: Speakers Bureau: Janssen, AZ, Takeda, Bei-
Gene, KaryoPharm
J. Sharman
Consultant or advisory role: Abbive, Astra Zeneca, BeiGene, Janssen,
Pfizer, Genentech, TG Therapeutics, BMS, Celgene
N. S. Trede
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
M. Youssef
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
J. Lymp
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
P. Shaughnessy
Other remuneration: Speakers Bureau: Sanofi, Kite
274 |OUTCOME DETERMINANTS OF COMMERCIAL CART
CELL THERAPY FOR LARGE BCELL LYMPHOMA: RESULTS OF
THE GLA/DRST REAL WORLD ANALYSIS
P. Dreger
1
, P. Martus
1
, U. Holtick
1
, F. Ayuk
1
, E. M. WagnerDrouet
1
,
G. Wulf
1
, R. Marks
1
, O. Penack
1
, C. Koenecke
1
, M. von Bonin
1
, B. von
Tresckow
1
, M. Stelljes
1
, C. Baldus
1
, V. Vucinic
1
, D. Mougiakakos
1
, M.
Topp
1
, D. Wolff
1
, R. Schroers
1
, M. Schmitt
1
, T. Schmitt
1
, C. Lengerke
1
,
S. Thomas
1
, D. W. Beelen
2
, W. Bethge
1
1
German Lymphoma Alliance, Working Group Hematopoietic Cell
Therapy, Muenster, Germany,
2
German Registry for Stem Cell
Transplantation, DRST, Essen, Germany
Introduction: In Germany, commercial CART cell therapies are
registered with the German Registry for Stem Cell Transplantation
(DRST), which is the National partner organization of the EBMT
registry. Here, we present the first risk factor analysis of standardof
care (SOC) CART cell therapies for large Bcell lymphoma (LBCL)
based on DRST data.
Methods: Eligible were all patients who received SOC axicel (A) or
tisacel (T) for treatment of LBCL until December 2020 and were
registered with the DRST. Baseline patient, disease, and treatment
data were collected from MEDA Cellular Therapy forms. Centers
were contacted to provide additional course and followup infor-
mation. Main outcomes analyzed were toxicities, response, and sur-
vival endpoints. Predictors of progressionfree survival (PFS) were
analyzed by uniand multivariate comparisons.
Results: A total of 267 patients were enrolled by 18 centres (A
137, T 130). Compared to the approval trials, patients were of
relatively poor risk with 51% being ZUMA1ineligible, 71% pre-
senting with elevated LDH at lymphodepletion, 79% needing
bridging, and 80% having received 3 pretreatment lines. Whereas
A and T cohorts were comparable for age, sex, LDH, and pre-
treatment, the T group contained significantly larger proportions of
patients with unfavorable IPI, poor performance status, and need
for bridging. Both CRS and neurotoxicity were significantly more
common after A compared to T. 17 grade 5 toxicities occurred (A
12, T 5; ns), largely due to infections. Overall and complete
response rates to A and T were 77% and 47% (p <0.0001), and
40% and 25% (p =0.013), respectively. With a median followup
of 6.7 months, progression/relapse occurred in 71 (52%) and 91
(72%) patients after A and T, respectively (p =0.0027). Of note,
17 events were observed beyond 6 months, and 3 beyond 12
months post dosing. PFS, overall survival, and nonrelapse mor-
tality (NRM) 12 months after dosing of A and T were 32% and
15% (p =0.0018), 54% and 47% (ns), and 8% and 4% (ns),
respectively. Other significant risk factors for PFS on univariate
analysis were elevated LDH, need for bridging, and >3 pretreat-
ment lines. The adverse impact of T, LDH, and bridging on PFS
remained significant after multivariable adjustment for confounders
(HR 1.51 (95%CI 1.122.04), 1.55 (1.12.18), and 1.66 (1.122.46),
respectively).
Conclusion: The results of this large GLA/DRST analysis on SOC
CART cell treatment of LBCL are impaired by an abundance of
relapse and NRM events beyond the 6month landmark not observed
in other studies. The enrichment of poorrisk features in our sample
might have contributed to this finding. Determinants of an adverse
outcome are elevated LDH, bridging, and use of T. The short follow
up and the limitations of a registry study have to be taken into
account.
370
-
SUPPLEMENT ABSTRACTS
Keywords: Cellular therapies, Immunotherapy
Conflicts of interests pertinent to the abstract
P. Dreger
Consultant or advisory role: Gilead, Novartis, BMS, bluebird bio,
Takeda
275 |FIRST REPORT OF THE REALLIFE PROSPECTIVE
OBSERVATIONAL STUDY “CART CELL IN DIFFUSE LARGE BCELL
AND PRIMARY MEDIASTINAL LYMPHOMAS” OF THE ITALIAN
SOCIETY OF HEMATOLOGY
A. Chiappella
1
, A. Guidetti
1
, A. Dodero
1
, S. Bramanti
2
, P. Zinzani
3
, A.
Santoro
2
, B. Casadei
3
, A. Di Rocco
4
, M. Carrabba
5
, P. Chiusolo
6
, M.
Martino
7
, A. M. Barbui
8
, M. C. Tisi
9
, R. Miceli
10
, C. Carniti
11
, P.
Corradini
12
1
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Hematology
and Stem Cell Transplantation, Milano, Italy,
2
Humanitas Clinical and
Research Center, IRCCS, Hematology, Rozzano, Italy,
3
University of
Bologna, Institute of Hematology “Seràgnoli”, Bologna, Italy,
4
'Sapienza'
University of Rome, Department of Translational and Precision Medicine,
Roma, Italy,
5
San Raffaele Hospital, IRCCS, Hematology and Bone Marrow
Transplantation Unit, Milano, Italy,
6
Fondazione Policlinico Universitario
A. Gemelli IRCCS; Università Cattolica del Sacro Cuore, Department of
Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia;
Hematology Section, Department of Scienze Radiologiche ed
Ematologiche, Roma, Italy,
7
Grande Ospedale Metropolitano “Bianchi
MelacrinoMorelli”, Stem Cell Transplant and Cellular Therapies Unit,
Reggio Calabria, Italy,
8
Azienda Socio Sanitaria Territoriale (ASST),
Ospedale Papa Giovanni XXIII, Hematology Unit, Bergamo, Italy,
9
San
Bortolo Hospital, Cell Therapy and Hematology, Vicenza, Italy,
10
Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano, Unit of
Clinical Epidemiology and Trial Organization; Department of Applied
Research and Technological Development, Milano, Italy,
11
Fondazione
IRCCS Istituto Nazionale dei Tumori, Milano, Italy, Laboratory of
Hematology, Division of Hematology and Stem Cell Transplantation,
Milano, Italy,
12
Chair of Hematology, University of Milano; Fondazione
IRCCS Istituto Nazionale dei Tumori di Milano, Division of Hematology
and Stem Cell Transplantation, Milano, Italy
Introduction: Axicabtagene ciloleucel (axicel) and tisagenlecleucel
(tisacel) are antiCD19 chimeric antigen receptor T cells (CART)
that proved very effective in relapsed/refractory (R/R) diffuse large
Bcell (DLBCL) and primary mediastinal Bcell lymphoma (PMBCL). to
evaluate safety and efficacy of axicel and tisacel.
Methods: The Italian Society of Hematology (SIE) is conducting a
prospective observational trial aimed to: 1. register all DLBCL and
PMBCL patients (pts) candidate to CART in the Italian authorized
centers; 2. evaluate the intention to treat overall response rate (ORR,
complete [CR] and partial response [PR]), duration of response
(DOR), progression free survival (PFS) and overall survival (OS); 3.
evaluate safety in terms of cytokine release syndrome (CRS), immune
effector cellassociated neurotoxicity syndrome (ICANS) and long
term cytopenia; 5. evaluate different CART products. The study
was approved by ethics committees.
Results: Since March 2019 to January 2021, 126 pts were leuka-
pheresed and 113 infused. Clinical characteristics of the 113 infused
pts were: median age 53 years (1970), stage III/IV 77 (68%), 81
(72%) primary refractory; median number of prior lines was 3 (27),
including 33 (29%) prior autologous stem cell transplantation. For
histologies, 59 (52%) were DLBCL, 18 (16%) highgrade Bcell
(HGBCL), 23 (20%) PMBCL, 13 (12%) transformed Follicular (tFL).
Bridging therapy was delivered to 97 pts (86%) and all pts received
lymphodepletion. Fiftynine (52%) infused axicel and 54 (48%) tisa
cel. Median followup time for infused pts was 6.9 months (IQR: 3.13
11.78). At 30days after the infusion, all the pts were evaluable for
response: 45 (40%) CR, 35 (31%) PR, with ORR of 71%. For the
evaluable pts, DOR was 73% (95%CI:6285) at 6months and 58%
(95%CI:4477) at 12months. In the whole series, 6 and 12months
PFS were 54% (95% CI:4565) and 46% (95%CI:3559); 6 and 12
months OS were 80% (95%CI:7188) and 75% (95%CI:6586),
respectively. With the limitation of small number, 6months PFS were
48% for DLBCL, 62% for HGBCL, 66% for PMBCL and 59% for tFL;
6months OS by histotype were 78% for DLBCL, 80% for HGBCL,
80% for PMBCL and 92% for tFL. No differences between axicel and
tisacel were reported. Severe (grade 34) CRS was observed in only
6 (5%) pts, and severe ICANS in 11 (10%). Sixtyone (54%) pts
received tocilizumab and 38 (34%) steroids. Cytopenia beyond 30
days was reported in 30 (27%) pts; 27 of them (24%) experienced
viral or bacterial infections. No toxic deaths were recorded.
Conclusions: In the reallife, axicel and tisacel showed an ORR
similar to those of the registrative trials, even if almost all pts un-
derwent bridging therapy. The response rate is similar across histo-
types and between products. CART toxicity is manageable, relapse
beyond 6 months is a rare event. Cytopenias as well as infections are
an emerging problem in reallife setting.
EA previously submitted to EHA 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Cellular ther-
apies, Immunotherapy
No conflicts of interests pertinent to the abstract.
276 |FDGPET IMAGING AND RADIOMICS IN RESPONSE
ASSESSMENT OF LYMPHOMA PATIENTS UNDERGOING CAR T
CELL THERAPY
B. Casadei
1
, A. Paccagnella
2
, A. Farolfi
2
, L. Argnani
1
, C. Malizia
2
, G.
Paolani
3
, M. Santoro
3
, G. Della Gala
3
, S. Strolin
3
, L. Strigari
3
, S.
Guadagnuolo
1
, F. Bonifazi
4
, S. Fanti
3
, P. L. Zinzani
1
1
IRCCS Azienda OspedalieroUniversitaria di Bologna Istituto di Emato-
logia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diagnostica
e Sperimentale Università di Bologna, n/a, Bologna, Italy,
2
IRCCS Azienda
OspedalieroUniversitaria di Bologna, Nuclear Medicine Unit, Bologna,
Italy,
3
IRCCS Azienda Ospedaliera Universitaria Bologna, Medical Physics
SUPPLEMENT ABSTRACTS
-
371
Department , Bologna, Italy,
4
IRCCS Azienda Ospedaliera Universitaria
Bologna, Hematology, Bologna, Italy
Background: Radiomics involves the extraction of quantitative fea-
tures from medical images, such as positron emission tomography
(PET), representing potential surrogate markers of the lymphoma
phenotypes. Chimeric antigen receptorT (CART) cell therapy has
revolutionized the treatment of large B cell lymphomas. Unfortunately,
the relapse rate is around 30–60% and almost 20% of patients develop
grade >3 Cytokine Release Syndrome (CRS). In this setting, it is of
critical importance the early identification of relapsed/refractory pa-
tients and of whom can develop CRS. Primary aim was to early predict
the response to CART based on metabolic features extracted from the
clinical and baseline FDGPET. Secondary aim was to determine the
presence of CRS from the clinical and imagebased features.
Methods: From September 2019 to December 2020, 20 patients
were treated with CAR Tcell therapy. All patients underwent FDG
PET/CT evaluation at baseline (PET_0) and 1 month after (PET_1)
CAR Tcell infusion. PET_0 semiquantitative parameters, namely
SUVmax, metabolic tumor volume (MTV), total lesion glycolysis
(TLG), were calculated. Pyradiomics library was used for the extrac-
tion of 105 radiomics features from each image. Univariate analysis
on both clinical and radiomics features was performed to evaluate
the correlation with the outcome. A generalized linear model (GLM)
was trained to predict the outcome and ROC analysis was used to
assess the prediction capability.
Results: Patients had a wide range of baseline disease burden, with a
median MTV of 129 ml (range: 55916) and a median TLG of 971 Bq
(range: 2132241). Ten (53%) patients achieved a complete (CR) and
9 (47%) a partial response (PR). Of these 9 patients, 6 underwent re
evaluation at 3 months: 1 converted to CR, 4 had a progression to
PD and 1 patient maintained the PR. No correlation was found be-
tween baseline MTV and TLG and tumor response at PET_1, while
they were significantly associated with the severity of CRS (p <0.5)
(AUC: 0.95; 95%CI: 0.871 for MTV and AUC: 0.92; 95%CI: 0.791
for TLG). Two radiomics features, Kurtosis and Median, were sta-
tistically significantly correlated with response at PET_1, while the
surface area was statistically significantly correlated with moderate/
severe CRS. In the GLM, only Median was a prognostic factor of
response, with an AUC of 0.81 (p <0.002) while surface area was a
prognostic factor of moderate/severe CRS with an AUC of 0.81 (p <
0.009).
Conclusions: Baseline FDGPET radiomics features were able to
differentiate between early responder and nonresponder patients
treated with CART and between patients with/without moderate/
severe CRS; MTV and TLG were also associated with CRS. Further
correlation between FDGPET_0 radiomics features/clinical baseline
characteristics and patients’ outcome (including progression free
survival) will be investigated with larger cohort and longer followup.
Keywords: Diagnostic and Prognostic Biomarkers, PETCT, Cellular
therapies
No conflicts of interests pertinent to the abstract.
277 |QUANTITATIVE METABOLIC PARAMETERS
EVALUATION IN PATIENTS WITH AGGRESSIVE BCELL
LYMPHOMAS TREATED WITH ANTICD19 CAR TCELLS
A. Guidetti
1
, A. Dodero
1
, G. Argiroffi
2
, P. Verderio
3
, A. Lorenzoni
2
, A.
Chiappella
1
, C. Carniti
1
, E. Seregni
2
, s. Pizzamiglio
3
, A. Alessi
2
, P.
Corradini
1
1
Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology, Milano,
Italy,
2
Fondazione IRCCS Istituto dei Tumori, Nuclear Medicine, Milano,
Italy,
3
Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of
Bioinformatics and Biostatistics, Milano, Italy
Introduction: Autologous antiCD19 chimeric antigen receptor (CAR)
Tcell therapy is an effective therapy for relapsed/refractory (R/R)
aggressive Bcell lymphomas and predictive biomarkers of response
are required. Quantitative metabolic parameters from 18FDG PET
CT scan are emerging tools able to predict outcome in aggressive
lymphomas, but their value in the CAR T setting is still under
investigation.
Methods: We conducted an observational prospective study of 34
patients affected by R/R aggressive lymphomas receiving axicabta-
gene ciloeucel (axicel) or tisagenlecleucel (tisacel); PETCT was
evaluated before lymphodepletion, at 1 and 3 months post infusion.
Quantitative PET parameters were computed with PETVCAR
software (GE Healthcare) on dedicated workstations. Contours of
pathological lesions were delineated using two semiautomatic con-
touring system including percentage threshold of standardized up-
take value (SUVmax) (41%) and gradient based threshold (adaptive
iterative algorithm). SUVmax, SUVmean, Metabolic tumor volume
(MTV) and Total lesions glycolysis (TLG) were automatically recor-
ded. Total MTV (TMTV) and total TLG (TTLG) were calculated as
the sum of all individual lesions. A quantitative measure of intra-
tumoral heterogeneity (heterogeneity index, HI, SUVmax/SUVmean)
was also recorded. The goals were to determine whether PETCT
quantitative metabolic parameters could predict clinical response
as well as to explore the prognostic role of the early PETCT. To
these end univariate logistic and Cox regression models were
implemented.
Results: 34 patients were enrolled: 29 were evaluable, 5 were not
included in the analysis for extranodal localization of disease (bone).
Median age was 51 (range, 2270), 20 patients were affected by
diffuselarge Bcell lymphomas and 9 by primary mediastinal Bcell
lymphoma. Patients received treatment with axicel (n =18) or
tisacel (n =11) at physician discretion. Before infusion, 45% had high
LDH and 38% had bulky disease. At a median followup of 343 days
(IQR, 214482 days), 24 patients are alive and 5 died of disease
progression with an estimated PFS and OS of 39% (95%CI, 20%58%)
and 78% (95%CI, 55%91%), respectively. Clinical response at 1
month occurred in 55% of the patients (n =8 CR, n =8 PR); pro-
gressive disease at 3 months occurred in 1 pt in CR and in 4 in PR.
Baseline values of SUVmax, SUVmean, TTLG, TMTV, HI did not
correlate with clinical response and PFS. On the contrary, the
decrease of HI between baseline and 1 month were significantly
372
-
SUPPLEMENT ABSTRACTS
associated with response at 1 month (OddsRatio: 1.41; 95%CI: 1.02
1.93; p =0.035).
Conclusions: Baseline quantitative parameters did not correlate with
outcome suggesting that several others factors could influence the
response to CAR Tcells. The variation of metabolic heterogeneity
are strictly associated with response suggesting an important role of
early evaluation of disease after CAR Tcells infusion. A larger cohort
of patients and a validation group are needed in order to verify these
observations.
Keywords: PETCT
No conflicts of interests pertinent to the abstract.
278 |RESISTANCE OF BCELL LYMPHOMAS TO CART CELL
THERAPY IS ASSOCIATED WITH HISTOPHENOTYPICAL AND
GENOMIC TUMOR CHANGES WHICH CAN INDUCE PROFOUND
TRANSDIFFERENTIATION
C. Laurent
1
, M. Hamon
2
, C. Syrykh
3
, J. Adélaïde
4
, A. Guille
5
, M.
Parrens
6
, P. Dartigues
7
, A. Bardet
8
, L. Mescam
8
, J.M. Schiano De
Colella
8
, P. Sujobert
9
, C. Besson
2
, D. Birnbaum
5
, L. Xerri
8
1
Oncopole, Pathology, Toulouse, France,
2
Hopital André Mignot,
Pathology, Versailles, France,
3
Oncopole, pathology, Toulouse, France,
4
IPC, Predictive Oncology/ CRCM, Inserm, CNRS , AMU, Marseille, France,
5
CRCM, Predictive oncology, Marseille, France,
6
Hopital hautLévéque,
Pathology, Bordeaux, France,
7
IGR, Pathology, Villejuif, France,
8
Institut
PaoliCalmettes, pathology, Marseille, France,
9
CHU LyonSud, Hématol-
ogy, PierreBénite, France
Backgroud: Chimeric Antigen Receptor (CAR) Tcell therapy target-
ing CD19 has shown efficacy against Bcell lymphomas, but a sig-
nificant proportion of patients will eventually relapse. The
histopathological and molecular changes associated with treatment
failure are still largely unknown.
Methods: To clarify this point, we have analyzed 16 sequential tumor
samples from 6 patients (pts) prior CART therapy (PreCAR) and at
relapse (PostCAR), using immunohistochemistry (IHC), FISH, array
CGH (CGH), Large Panel Next Generation Sequencing (NGS), RNA
sequencing (RNA seq) and genome–scale DNA methylation (METH).
Results: The initial diagnosis was diffuse large Bcell lymphoma
(DLBCL, n =5) and Burkitt's lymphoma (BL, n =1). In 3/6 pts
(DLBCLs), the morphological, phenotypical and FISH patterns
remained mostly similar in paired sequential samples, except for a
slight decrease in CD19 staining whereas CD20, CD79A and PAX5
remained unchanged. These 3 cases exhibited isolated rearrange-
ments of BCL2,BCL6 and MYC, respectively. CGH showed an increase
in the number of chromosomal alterations in PostCAR. NGS showed
the occurrence of additional pathogenic variants in PostCAR,
including the PI3K pathway (PIK3R1, PIK3R2, PIK3C2G) and genes
associated with aggressive tumor behavior (INPP4B, SYNE1,
TBL1XR1).
In contrast, the 3 remaining cases (2 DLBCLs and 1 BL) showed
loss or drastic decrease of most Bcell markers including CD19,
CD20, CD79A and PAX5. In 2 cases, the relapse samples displayed a
complete morphophenotypic shift, with emergence of Tcell markers
(CD2, CD3 and CD7) in 1 case; or expression of histiocytic markers
(CD163, CD68) together with a histiocytelike morphology in the
other case. Clonality analysis showed identical clonal IGH rear-
rangements in sequential samples from both cases. NGS showed the
occurrence of KRAS,MAP2K1 and SF3B1 mutations in PostCAR. A
PAX5 mutation was detected in the PostCAR sample with aberrant
Tcell phenotype, which also showed reduced mRNA expression of
most Bcell genes and increased methylation of the corresponding
promoters.
Conclusions: These preliminary results indicate that CART resis-
tance in BNHLs can be associated with profound dysregulation of B
cell differentiation and upregulation of genes involved in tumor
proliferation. The occurrence of mutations in the PI3K and KRAS
pathways suggests that appropriate targeted therapies could be
useful in CART resistant pts. PostCAR aberrant Tcell phenotype
brings a proof of concept of in vivo transdifferentiation from Bcell
into Tcell lymphoma program due to therapeutical selection pres-
sure. Pathologists have to be aware of such unexpected features as
potential diagnostic pitfalls.
Keywords: Pathology and Classification of Lymphomas
No conflicts of interests pertinent to the abstract.
279 |IN VITRO ANALYSIS PREDICTS CLINICAL RESPONSE OF B
CELL LYMPHATIC MALIGNANCIES TO CD19 CART CELLS:
PHENOTYPIC, TRANSCRIPTIONAL AND FUNCTIONAL STUDY
K. Beider
1
, M. J. Besser
2
, E. Jacoby
3
, J. Schachter
4
, V. Voevoda
Dimenshtein
1
, E. Rosenberg
1
, O. Ostrovsky
1
, I. Danylesko
1
, A. Shi-
moni
1
, A. Avigdor
1
, A. Nagler
1
1
Sheba Medical Center, Hematology Division, Ramat Gan, Israel,
2
Sheba
Medical Center, Ella Institute of ImmunoOncology, Ramat Gan, Israel,
3
Sheba Medical Center, Department of Pediatrics, The Edmond and Lily
Safra Children's Hospital, Ramat Gan, Israel,
4
Sheba Medical Center, Ella
Institute of ImmunoOncology, Ramat Gan, Israel
In spite of high rates of overall response to chimeric antigen receptor
(CAR) T cell therapy its curative potential is jeopardized by exhaus-
tion of the CAR T cells conceivably mediated by the immunosup-
pressive tumor microenvironment and excessive antigen exposure.
However, cellular and molecular predictors of clinical response are
not fully elucidated.
We performed immunophenotypic and transcriptomic analysis
of T cells from patients (pts) with relapsed/refractory B cell ma-
lignancies (n39: NHL28, ALL5, CLL6) treated with locally pro-
duced CD19 CAR T cells in correlation with pts’ day 28 clinical
response. Intact CD3
+
T cells from peripheral blood (PB) samples
SUPPLEMENT ABSTRACTS
-
373
pre Flu/Cy lymphodepletion and the manufactured CAR T cells
were analyzed. The CD8
+
and CD4
+
T cells were individually
assessed by a panel of 17 immune surface markers identifying
different T cell subsets. Transcriptional signature was assessed by
NanoString technology.
Phenotypic signature identified a higher proportion of exhausted
CD57
+
CD39
+
cytotoxic CD8
+
cells in CAR T products of non
responders (NR) in comparison to pts with complete response (CR).
Furthermore, CD8
+
CAR T cells of NR were characterized by CD28
and IL7R loss, and lower levels of CCR7. Expression of T cell
checkpoint inhibitor PD1 was high in exhausted CD8
+
cells. Impor-
tantly, higher proportion of exhausted cytotoxic CD8
+
cells was
detected in PB of NR comparing to CR pts, suggesting the association
of CAR T exhaustion with a dysfunctional phenotype of pts’ T cells. In
contrast CD4
+
cells demonstrated low frequency of exhausted
phenotype both in the PB as well as the CAR T product from both NR
and CR pts achieving CR, indicating that CD4
+
T cells are less prone
to exhaustion suggesting better persistence of CD4 CAR T cells
following antigen exposure.
The transcriptional signature of the CAR T products overlaid
with the phenotypic characterization. Higher levels of IL7R, CD7,
BATF3, IL15, FOS, MYC, CD69 and CD27 genes were detected in
CAR T cells of CR pts. In contrast, CAR T cells from NR were enriched
with terminally exhausted population, upregulating CD57, TOX,
EOMES, GZMB, GZMA, GZMH, CCL4 and LAG3 genes.
Finally, the functional capacity of the CAR T cells was
evaluated in coculture experiments with CD19
+
Raji cells. Stim-
ulation with CD19
+
targets induced proliferation and cytokine
secretion in the CAR T effectors. Importantly, reduction of both
proliferation as well as IL2 secretion correlated with the
exhaustion signature.
Overall, these results reveal potential cellular and molecular
mediators of resistance, identifying an enrichment of terminally
exhausted CD8+T cells as a main feature observed in PB and CAR T
products of resistant pts. Delineating these mechanisms may guide
future T cells engineering studies to enhance the efficacy and dura-
bility of CAR T therapy in B cell malignancies.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
MISCELLANEOUS
280 |GENDER DISPARITIES IN QUALITY OF LIFE OF FRENCH
PATIENTS ONE YEAR AFTER THE DIAGNOSIS OF LYMPHOMA. A
LYSA STUDY
A.C. Paunescu
1
, J. Paget
2
, C. Copie Bergman
3
, S. Malak
4
, S. Le
Gouill
5
, V. Ribrag
6
, K. Bouabdallah
7
, D. Sibon
8
, G. Rumpold
9
, M.
Preau
10
, N. Mounier
11
, C. Haioun
12
, F. Jardin
13
, C. Besson
14
FIGURE 1 (A) Exhausted phenotype of infused CAR T products and peripheral blood samples prior to lymphodepletion. NR non
responders (n =15), CRcomplete responders (n =24). (B) Transcriptional signature of infused CAR T products, NR and CR, analyzed by
NanoString platform. (C) Proliferation of CD8+CAR T cells upon stimulation with CD19+target cells(Raji) oppositely correlates with CD8+
exhaustion and directly correlates with interleukin2(IL2) secretion.
374
-
SUPPLEMENT ABSTRACTS
1
Gustave Roussy, Epidemiology, Villejuif, France,
2
Lysarc, Lysarc, Lyon,
France,
3
CHU Mondor, pathology, Créteil, France,
4
Curie, Hematology,
SaintCloud, France,
5
CHU Nantes, Hematology, Nantes, France,
6
Gustave Roussy, Hematology, Villejuif, France,
7
CHU Bordeaux, Hema-
tology, Bordeaux, France,
8
CHU Necker, Hematology, Paris, France,
9
Medical University Innsbruck, Department of Medical Psychology, Inns-
bruck, Austria,
10
Université Lyon 2, GRePS, Lyon, France,
11
CHU Nice,
Hematology, Nice, France,
12
Henri Mondor University Hospital,
Lymphoid malignancies unit, Créteil, France,
13
Centre Henri Becquerel,
Hematology, Rouen, France,
14
CH Versailles, Hematology, Le Chesnay,
France
In France, Diffuse Large BCell Lymphoma (DLBCL) is the most
common subtype of nonHodgkin lymphoma (NHL). Healthrelated
quality of life (HRQoL) is a multidimensional concept including
physical, emotional, social functions, disease symptoms and side ef-
fects of treatments. Differences in HRQoL due to gender are little
explored in NHL. To investigate whether differences in HRQoL be-
tween women and men exist after diagnosis of their lymphoma, we
evaluated several facets of HRQoL.
One year after DLBCL diagnosis, 141 patients, enrolled in the
RT3 (Real Time Tailored Therapy) Study in 2018 and 2019, were
invited to answer selfadministrated European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire
Core 30 (EORTC QLQC30), Hospital Anxiety and Depression Scale
(HADS), and Post Traumatic Growth Inventory (PTGI) questionnaires.
Adjusted means and their 95% confidence intervals (95% CI) were
calculated in multivariate linear regression models, and compared
between female and male survivors.
68% of eligible patients agreed to participate and 82% of them
answered all questionnaires. Participants and non participants did
not differ significantly regarding sociodemographic and clinical var-
iables, as did female and male participants (mean age of 58.5 years).
The adjusted means of the EORTC QLQC30 subscales were not
different between women and men, excepting for insomnia, signifi-
cantly higher in women than in men (38.3 vs. 17.2, P=0.04). Anxiety
scores of HADS and several subscales of PTGI were significantly
higher in women compared to men (Table).
Women seem to be more prone to anxiety, insomnia, and a post
traumatic growth after DLBCL than men. The explanation of these
disparities is unclear. Specific qualitative approaches should be set up
for women with DLBCL.
The research was funded by: Calym
Keywords: Cancer Health Disparities
No conflicts of interests pertinent to the abstract.
281 |CARDIOTOXICITY RISK IN PATIENTS WITH NON
HODGKIN LYMPHOMA RECEIVING EPOCH AFTER PRIOR
ANTHRACYCLINE EXPOSURE
M. J. Buege
1
, P. H. Dao
1
, E. Drill
2
, S. M. Horwitz
3
, A. LeVoir
1
, T. Pak
1
,
T. J. Peterson
1
, M. J. Matasar
3
1
Memorial Sloan Kettering Cancer Center, Pharmacy, New York, USA,
2
Memorial Sloan Kettering Cancer Center, Epidemiology & Biostatistics,
New York, USA,
3
Memorial Sloan Kettering Cancer Center, Medicine, New
York, USA
Introduction: Anthracyclines are utilized in many chemotherapy reg-
imens for lymphoma and carry a doserelated risk of cardiotoxicity.
Reducing peak cardiomyocyte anthracycline concentrations with
continuous infusion strategies reduces the risk of cardiotoxicity. The
infusional chemotherapy regimen EPOCH (etoposide, prednisone,
vincristine, cyclophosphamide, and doxorubicin) is frequently used in
both frontline and relapsed/refractory settings for aggressive non
Comparisons of psychometric scales to gender after DCBCL
SUPPLEMENT ABSTRACTS
-
375
Hodgkin lymphomas (NHLs). Whether through treatment for previous
malignancies or prior lines of treatment for lymphoma, a subset of
patients with NHL who receive EPOCH have had prior exposure to
bolus anthracycline regimens. Cardiac outcomes in patients who
receive EPOCH following previous anthracycline exposure remain
largely unexplored.
Methods: We reviewed adults treated for NHL with EPOCH, with or
without rituximab, at Memorial Sloan Kettering Cancer Center be-
tween 2004 and 2019 who had anthracycline exposure prior to
EPOCH. Patients who had a clinical diagnosis of heart failure at
initiation of EPOCH or did not have baseline evaluation of left ven-
tricular ejection fraction (LVEF) within 3 months prior to initiating
EPOCH were excluded. The primary outcome was incidence of
composite cardiac events consisting of LV dysfunction, heart failure,
arrhythmia, or cardiac death.
Results: Among 140 eligible patients (Table 1), the median age was
58 years; the most common diagnosis was diffuse large Bcell lym-
phoma (79%). Inclusive of EPOCH, patients received a cumulative
median doxorubicinequivalent dose of 364mg/m
2
(Shankar SM,
et al. Pediatrics. 2008;121:e38796), and exposure was 400mg/m
2
in 42%. Six patients (4%) had exposure to dexrazoxane at any time.
Median time between initiation of EPOCH and the most recent
available evaluation of LVEF was 2 months (range, 0 to 140 months).
At median followup from initiation of EPOCH of 36 months, 23
cardiac events were noted in 20 (14%) patients. Cumulative inci-
dence of cardiac events limited to LV dysfunction or heart failure
was 9% at 120 months, with most events occurring after the first
year (Figure 1). Risk factor analysis, including impact of cumulative
anthracycline dose and characteristics associated with risk of cardiac
events, is underway and will be included in the final presentation.
Conclusions: In this cohort, which represents the largest experience
with EPOCH chemotherapy following prior bolus anthracycline, cu-
mulative incidence of cardiac events was low. Cumulative incidence
of LV dysfunction or heart failure was particularly low, suggesting
infusional anthracycline administration may mitigate risk despite
TABLE 1*(n =140)Sample characteristics and cardiac outcomes
FIGURE 1 Cumulative incidence of cardiac events
376
-
SUPPLEMENT ABSTRACTS
prior exposure. Risk may be underestimated due to limited duration
of LVEF monitoring after EPOCH initiation, although the low rate of
clinically evident cardiac events supports the safety of EPOCH
despite prior bolus anthracycline therapy.
Keywords: Late Effects in Lymphoma Survivors, Aggressive Bcell
nonHodgkin lymphoma, Aggressive Tcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
S. M. Horwitz
Consultant or advisory role: ADCT Therapeutics, Aileron, Corvus,
FortySeven, Innate Pharma, KyowaHakkaKirin, Millenium/Takeda,
Mundipharma, Portola, Seattle Genetics
Research funding: ADCT Therapeutics, Aileron, Celgene, Forty
Seven, Infinity/Verastem, KyowaHakkaKirin, Millenium/Takeda,
Seattle Genetics, Trillium
M. J. Matasar
Consultant or advisory role: Genentech, Bayer, Merck, Juno, Roche,
Teva, Rocket Medical, Seattle Genetics
Honoraria: Genentech, Roche, Bayer, Pharmacyclics, Janssen, Seattle
Genetics, GlaxoSmithKline
Research funding: Genentech, Roche, GlaxoSmithKline, Bayer, Phar-
macyclics, Janssen, Rocket Medical, Seattle Genetics
Educational grants: Genentech, Roche, Seattle Genetics, Bayer
282 |BURDEN OF LYMPHOMA IN CHINA, 19902019: AN
ANALYSIS OF GLOBAL BURDEN OF DISEASES, INJURIES, AND
RISK FACTORS STUDY 2019
W. Liu
1
, J. Liu
2
, Y. Song
1
, X. Wang
1
, L. Mi
1
, C. Cai
3
, D. Zhao
4
, L. Wang
2
,
J. Ma
4
, J. Zhu
1
1
Peking University Cancer Hospital & Institute, Department of Lymphoma,
Beijing, China,
2
National Center for Chronic and Noncommunicable
Disease Control and Prevention, Chinese Center for Disease Control and
Prevention, National Center for Chronic and Noncommunicable Disease
Control and Prevention, Beijing, China,
3
Beijing Institute of Survey and
Mapping, Beijing Municipal Key Laboratory of Urban Spatial Information
Engineering, Beijing Institute of Survey and Mapping, Beijing, China,
4
Harbin Institute of Hematology & Oncology, Harbin Institute of
Hematology & Oncology, Harbin, China
Background: China is facing the aggravating disease burden of lym-
phoma. However, the accurate information about lymphoma burden
at national and provincial levels is limited.
Methods: Following the general analytical strategy used in
Global Burden of Diseases, Injuries, and Risk Factors Study 2019,
the age, sexand provincespecific incidence, mortality and preva-
lence of Hodgkin lymphoma (HL) and nonHodgkin lymphoma (NHL)
were analyzed. Lymphoma burden was assessed by methods of
incidence, mortality, prevalence and disabilityadjusted life years
(DALYs).
Results: The estimated number and agestandardized rates of DALYs
per 100,000 population were 86,171.85 and 4.95 for HL, and
1,306,247.77 and 71.00 for NHL, respectively. There were estimated
9,470 new cases and 2,710 deaths of HL, and 91,950 new cases and
44,310 deaths of NHL. Older individuals had higher lymphoma burden
with a peak of the agespecific DALYs rates reached at the age group
7074 for both HL and NHL. The agestandardized DALYs rates in
males was about 2 folds higher than that in females. Moreover, dis-
parities in lymphoma burden was observed across provinces. Between
1990 and 2019, the burden of HL kept a downward trend with a
decrease of 57.8% in the DALY number and 74.4% in the age
standardized DALYs rates, while the burden of NHL aggravated with
an increase of 100.9% in the DALY number and 15.6% in the age
standardized DALYs rates.
Conclusion: Burden of lymphoma showed heterogeneous change
pattern varied by sex, age, and provinces, with a steady improvement
for HL and a fluctuant change for NHL.
Keywords: Hodgkin lymphoma, NonHodgkin (Pediatric, Adolescent,
and Young Adult)
No conflicts of interests pertinent to the abstract.
283 |IMPACT OF THE COVID19 PANDEMIC ON THE
DIAGNOSIS OF MATURE LYMPHOID NEOPLASMS IN BELGIUM:
RESULTS FROM THE BELGIAN CANCER REGISTRY
H. AntoinePoirel
1
, F. Calay
1
, T. Tambuyzer
1
, P. Denolf
1
, L. Van
Eycken
1
1
Belgian Cancer Registry, BCR, Brussels, Belgium
Introduction: Health care in Belgium was affected by the corona
pandemic and the corresponding measures taken by the govern-
ment since March 2020. The aim of this study is to make an esti-
mate of the decrease in the number of new diagnoses of
mature lymphoid neoplasms (MLN) due to the COVID19 crisis in
Belgium.
Methods: For its standard cancer reporting, the Belgian Cancer
Registry uses two data sources:
The oncological care programs from the hospitals provide
structured data (‘clinical network’)
The pathology laboratories deliver structured files and reports
(‘pathology network’)
Thanks to expedited deliveries of data by the pathology network
between January and September 2020, the Belgian Cancer Registry
was able to make an estimation of the decline in the number of di-
agnoses by types of MLN.
Since estimates were only based on pathology data and to pre-
vent bias, all results are shown as a relative ratio between the new
cancer diagnoses for incidence years 2020 and 2019. The ratios for
the months January and February, both prior to the start of the
COVID19 pandemic, were expected to be around 100%. Decline =
ratio 100%.
SUPPLEMENT ABSTRACTS
-
377
Results: After a strong decline by 28% during the first wave (March
May 2020) when compared to MarchMay 2019, the total diagnosis
of MLN reported by the pathology network stabilized around normal
values compared to 2019 levels, leading to an incomplete recovery
by end September 2020 (12%).
Variable effect by age group
Although the 2 adult age groups, 2079 vs 80+, exhibited the
same reduction of 28% during the MarchMay period, a partial re-
covery was observed for the 2079 age group (+4%) during the
following JuneSeptember period while the older population showed
a persistent reduction (9%), leading to an overall decline of 16% for
the 80+compared to 10% for the 2079 age group.
Although subject to a low number of cases, there was no evi-
dence of a decline in children and adolescents up to 19 years of age.
Variable effect by MLN type
Among Bcell MLN, the largest decrease by September was
observed for mature Bcell leukemias (MarchSept: 28%; March
May: 43%). The decrease was smaller for plasma cell neoplasms
(18%; 34%), other indolent lymphomas (14%; 40%) and Hodgkin
lymphoma (6%; 30%) while no evidence of decline for the more
aggressive MLN (DLBCL and Burkitt lymphoma), except for 80+
(MarchSept: 13%).
The strongest rebound in diagnosis was observed for mature T/
NK cell lymphomas which completely recovered to above 2019 levels
(MarchMay: 22%, JuneSept: +25%).
Conclusion: This study with pathology data available until the end of
September suggests a heterogeneous impact of the COVID19 crisis
on the different types of MLN. The largest persistent declines are
observed for the more indolent MLNs, while the effect was very
limited for the highgrade Bcell lymphoid neoplasms, with exception
of the older population.
The impact over the whole year 2020 will be presented during
the meeting.
The research was funded by: Belgian Fondation Against Cancer
Keywords: Cancer Health Disparities, Pathology and Classification of
Lymphomas
No conflicts of interests pertinent to the abstract.
284 |IMPAIRED HUMORAL RESPONSE IN LYMPHOMA
PATIENTS SURVIVING THE ACUTE PHASE OF COVID19
C. Cattaneo
1
, V. Cancelli
1
, C. Pagani
1
, A. Ogna
1
, A. Tucci
1
, G. Rossi
1
,
V. Quaresima
2
, A. Sotttini
2
, K. Dobbs
3
, L. D. Notarangelo
3
, J. I.
Cohen
4
, P. D. Burbelo
5
1
ASSTSpedali Civili, Hematology, Brescia, Italy,
2
CREA (Centro Ricerca
AIL), ASST Spedali Civili di Brescia, Diagnostic Department, Brescia, Italy,
3
National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Laboratory of Clinical Immunology and Microbiology, Bethesda,
Maryland, USA,
4
National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Laboratory of Infectious Diseases, Bethesda,
Maryland, USA,
5
National Institutes of Health, National Institute of Dental
and Craniofacial Research, Bethesda, Maryland, USA
Introduction: The ability to generate an adequate and durable im-
mune response to SARSCoV2 in Bcell lymphoma patients (pts)
treated with immunochemotherapy is still unclear. We monitored
378
-
SUPPLEMENT ABSTRACTS
antibody levels during convalescence in COVID19 survivors with
lymphoma, compared to other hematologic diseases (HemD) and
healthy controls (Ctrls).
Methods: Seventeen pts with nonHodgkin lymphoma (NHL) [follic-
ular (FL): 9; diffuse large Bcell (DLBCL): 8] surviving the acute phase of
virologicproven COVID19 were evaluated at 3 timepoints (TP) after
nasal swab negativity: +1 (TP1), +3 (TP3), and +6 (TP6) months; 28 pts
affected by HemD (10 multiple myeloma, 8 chronic lymphoprolifer-
ative disorders, 10 myelodysplastic/chronic myeloproliferative syn-
dromes) and 17 Ctrls were also evaluated at the same TP. Antibody
(Ab) levels to nucleocapsid (NAb) and spike (SAb) virus proteins were
measured using a highly sensitive luciferaseimmunoprecipitation
system (LIPS) assay. Positive levels were 125000 LU for NAb and
45000 LU for SAb.
Results: Mean Nand SAb levels were lower in FL and DLBCL than in
other HemD pts, both at TP1 (NAb 1217517 vs 2205610 LU, p =0.03;
SAb 580444 vs 1184453 LU, p =0.049) and at TP3 (NAb 850510 vs
2094487 LU p =0.012, SAb 605284 vs 1230946 LU, p =0.074). At
TP6 NAb levels declined in all subgroups, while SAb levels remained
stable. At TP1, compared to HemD, significantly less FL and DLCBL pts
reached positive levels of NAb (93% vs 59% p =0.017) and of SAb
(86% vs 47%; P: 0.008). Positive levels of NAb and SAb were also
more frequent in Ctrls (100% and 87%; p =0.007 and 0.028) than in
NHL pts. Rates of seroprotection remained lower in NHL pts also at
TP3 and TP6. Rituximab (RTX) had been given to 14/17 NHL pts, either
6 months in 5 (prior RTX) or <6 months in 9 pts (ongoing RTX) before
Covid19 diagnosis. Ongoing RTX had a markedly negative effect on S
Ab levels since none of 9 patients seroconverted at TP1 compared to 5/
5 prior RTX pts (P =0.0005). No changes occurred in the rate of
seroprotected pts also at TP3 and TP6 except for 1 ongoing RTX pt who
reached protective levels at TP6 (see figure). Overall seroprotective Ab
at any TP were present in 2 of 18 determinations in ongoing RTX pts,
despite RTX treatment discontinuation, and in 15 of 15 determination
in prior RTX pts (p =0.0001).
Conclusions: In FL and DLC NHL pts the humoral immune response to
SARSCov2 is less effective than in other HemD and in Ctrls. However,
in seroconverted pts, SAb levels did not significantly decrease after 6
months. Ongoing RTX at Covid19 was detrimental in that it did not
allow to develop a humoral antiS immune response and lack of
seroconversion persisted in most pts longterm despite discontinuing
RTX. These data could be considered with regard to vaccination policy,
although larger studies are needed to confirm them.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Indolent non
Hodgkin lymphoma
No conflicts of interests pertinent to the abstract.
285 |MULTICENTER RETROSPECTIVE ANALYSIS OF RISK
FACTORS FOR MORTALITY OF COVID19 INFECTION IN
PATIENTS WITH LYMPHOMA
J. Kořen
1
, K. Steinerová
2
, A. Janíková
3
, D. Belada
4
, B. Hájková
5
, M.
Krčméryová
6
, V. Hanáčková
7
, B. Vacková
1
, P. Jindra
2
, M. Osovská
3
, E.
Svobodová
4
, L. Dlouhá
1
, P. Vodička
1
, M. Trně
1
1
1st Department of Medicine, Faculty of Medicine 1, Charles University,
General Hospital, Prague, Czech Republic, haematology, Prague, Czech
Republic,
2
Department of Haematology and Oncology, Charles University
Hospital Pilsen, Czech Republic, haematology anf oncology, Pilsen, Czech
Republic,
3
3Department of Internal Medicine, Hematology and Oncology,
University Hospital Brno and Faculty of Medicine, Masaryk University
Brno, Brno, Czech Republic, Hematology and Oncology, Brno, Czech
Republic,
4
4th Department of Internal Medicine Haematology, Charles
University, Hospital and Faculty of Medicine, Hradec Králové, Czech
Republic, haematology, Hradec Králové, Czech Republic,
5
Department of
Haematooncology, University Hospital Ostrava, Czech Republic,
haematology, Ostrava, Czech Republic,
6
1Internal Clinic of Hematology,
University Hospital Kralovske Vinohrady, Third Faculty of Medicine,
Charles University in Prague, Czech Republic, haematology, Prague, Czech
Republic,
7
Department of HematoOncology, Faculty of Medicine, Palacky
University and University Hospital Olomouc, Czech Republic, haematol-
ogy, Olomouc, Czech Republic
Covid 19 infection leads to significantly higher morbidity and mor-
tality among lymphoma patients (pts.) compared to immunocompe-
tent population. The majority of published data is based on the
cohorts diagnosed during the spring and early autumn 2020 Covid
19 outbreak. Here we present a retrospective analysis of mortality
SUPPLEMENT ABSTRACTS
-
379
data and risk factors in one of the largest groups of pts. with lym-
phomas described so far, with majority diagnosed in the second half
of 2020 and early 2021.
Patients and methods. A total of 360 pts. followed for lymphoma
and participated in NiHiL project in 7 centers in the Czech Republic
and with COVID19 diagnosis during the period from February 2020
to February 26 2021 were included. The lymphoma and COVID19
characteristics were analysed and descriptive stastistic were used.
The median age of the whole group was 65 years (1989), 58% of
them were men, and 55% pts were on the antilymphoma therapy. In
terms of lymphoma subtypes, there were 181 (50%) aggressive B
NHL, of which 127 patients with DLBCL and 47 with MCL. 107 pa-
tients (30%) with indolent BNHL, of which 62 patients with FL, 18
MZL, 9 SLL, 7 LPL. 27 (7.5%) patients with TNHL and 45 (12.5%)
with HL. The median followup from the diagnosis of COVID19 was
3 months (113), 48% of patients had to be admitted to the hospital.
Out of those who required hospitalization died 40% . Overall mor-
tality rate was 21%.
There was no difference in mortality between NHL subtypes,
while patients with HL had a significantly lower risk of mortality
(hazard ratio 0.32, 95% CI [0.158, 0.648], P 0.04). However, there
were fewer patients (44%) with HL on the active treatment of lym-
phoma, compared to the whole group of NHL (56%), in the group of
aggressive NHL even 64%. A lower median age of patients with HL
(47) may also contribute to this finding.
Active treatment of lymphoma at the time of infection repre-
sented a significantly higher risk of death (hazard ratio 2.25, 95% CI
[1.428, 3.546], P 0.001). We did not show a statistically significantly
higher mortality with rituximab containing regimens compared to
chemotherapy alone. A higher risk of mortality was demonstrated in
patients with relapsed, progressive disease (Hazard Ratio 2.08, 95%
CI [1.073, 4.034], P 0.01).
Our data confirm an increased risk of mortality, especially in
patients with NHL, compared to the general population. The slightly
lower risk of mortality compared to previously published data can be
explained by the higher incidence of cases with a milder course,
recorded for analysis, treated only on an outpatient basis for COVID
19, which did not require hospitalization. The higher risk for patients
in active treatment suggests the need for active immunization before
treatment, where possible, and the need for effective therapy in case
of infection during ongoing antitumor therapy, including the use of
monoclonal antibodies to treat COVID19 infection.
Keywords: Cancer Health Disparities
No conflicts of interests pertinent to the abstract.
286 |OUTCOMES OF PATIENTS WITH LYMPHOMA AND
COVID19: AN OBSERVATIONAL COHORT STUDY FROM
GELTAMO SPANISH GROUP
A. Martín GarcíaSancho
1
, M. Izuzquiza
2
, M. BastosOreiro
3
, M.
Baile
1
, S. Nistal
4
, M. Cortés
1
, A. JiménezUbieto
5
, B. Rey Búa
1
, H.
GuillénGarcía
6
, J. CannataOrtiz
7
, S. Novelli
8
, M. I. GómezRoncero
9
,
F. J. Peñalver
10
, E. M. González Barca
11
, M. Infante
12
, M. Jesús
Peñarrubia
13
, M. Franch
14
, C. AlonsoPrieto
15
, I. Zeberio
16
, B. Sán-
chezGonzález
17
, A. Muntañola
18
, F. HernándezMohedo
19
, X.
MartínMartitegui
20
, J. María Arguiñano
21
, R. del Campo
22
, L.
Escoda
23
, A. RoldánPérez
24
, Á. RamírezPayer
25
, H. Luzardo
26
, S.
Lorente
27
, M. SoléRodríguez
28
, P. Abrisqueta
2
, J. M. Sancho
14
1
Hospital Universitario de Salamanca and IBSAL, Hematology
Department, Salamanca, Spain,
2
Hospital Vall d’Hebron, Hematology
Department, Barcelona, Spain,
3
Hospital Gregorio Marañón, Hematology
Department, Madrid, Spain,
4
Hospital Universitario HLA Moncloa,
Hematology Department, Madrid, Spain,
5
Hospital 12 de Octubre,
Hematology Department, Madrid, Spain,
6
Hospital Universitario de
Guadalajara, Hematology Department, Guadalajara, Spain,
7
Hospital
Universitario La Princesa, Hematology Department, Madrid, Spain,
8
Hospital de la Santa Creu i Sant Pau, Hematology Department,
Barcelona, Spain,
9
Hospital Virgen de la Salud, Hematology Department,
Toledo, Spain,
10
Hospital Universitario Fundación Alcorcón, Hematology
Department, Alcorcón, Madrid, Spain,
11
Institut Català d’Oncologia,
Hospital Duran i Reynals, IDIBELL, Univertitat de Barcelona, Hematology
Department, Barcelona, Spain,
12
Hospital Infanta Leonor, Hematology
Department, Madrid, Spain,
13
Hospital Clínico Universitario de
Valladolid, Hematology Department, Valladolid, Spain,
14
Hospital
Germans Trias i Pujol, Hematology Department, Barcelona, Spain,
15
Hospital Arnau de Vilanova, Hematology Department, Valencia, Spain,
16
Hospital Universitario de Donostia, Hematology Department,
DonostiaSan Sebastian, Spain,
17
Hospital del Mar, Hematology
Department, Barcelona, Spain,
18
Hospital Universitario Mutua Terrassa,
Hematology Department, Terrassa, Barcelona, Spain,
19
Hospital Virgen
de las Nieves, Hematology Department, Granada, Spain,
20
Hospital
Universitario Cruces, Hematology Department, Bilbao, Spain,
21
Complejo
Hospitalario de Navarra, Hematology Department, Pamplona, Spain,
22
Hospital Son Llàtzer, Hematology Department, Palma de Mallorca,
Spain,
23
Institut Català d’Oncologia, Hospital Joan XXIII, Hematology
Department, Tarragona, Spain,
24
Hospital Infanta Sofía, San Sebastián
de los Reyes, Hematology Department, Madrid, Spain,
25
Hospital Central
de Asturias, Hematology Department, Oviedo, Spain,
26
Hospital Doctor
Negrín, Hematology Department, Las Palmas de Gran Canaria, Spain,
27
Hospital Vithas Xanit Internacional, Benalmádena, Hematology
Department, Málaga, Spain,
28
Hospital Juan Ramón Jiménez, Hematol-
ogy Department, Huelva, Spain
Introduction: COVID19 is thought to be more frequent and severe
in patients with cancer. Lymphoma patients may be especially
vulnerable, due to the immunodeficiency and immune dysregulation
caused by the lymphoma itself and the antitumor treatments. This
study describes the characteristics and outcomes of lymphoma pa-
tients after developing COVID19.
Methods: This is a retrospective multicentre study carried out in the
hospitals of the GELTAMO group, which included patients with a
histological diagnosis of lymphoma and confirmed SARSCOV2
infection before June 30
th
, 2020. The primary outcome was overall
survival (OS) 60 days after a COVID19 diagnosis.
380
-
SUPPLEMENT ABSTRACTS
Results: A total of 218 patients (median sage 69.5 [2194] years, 54%
male) were included; 100 patients had an indolent Bcell non
Hodgkin's lymphoma (NHL), 67 aggressive Bcell NHL, 19 mantle
cell lymphoma, 15 peripheral Tcell lymphoma, and 17 Hodgkin's
lymphoma. Patients had received a median of 1 line (07) of therapy,
and 44.9% were on active treatment at the time of COVID19
diagnosis. Only 6.4%, 1.8% and 0.9% of patients had received pre-
viously autologous stemcell transplantation, allogeneic SCT and
CART cell therapy, respectively. 89% of patients were hospitalized,
71% required oxygen, and 15% mechanical ventilation. With a me-
dian followup of 91.5 days (13203), 65 patients have died (60 from
COVID19, 4 from lymphoma, 1 due to other causes), with an esti-
mated 60day OS of 68.6% (95% CI 62.1–75.1) (figure 1A). In uni-
variate analysis, baseline characteristics associated with decreased
OS were age 70 years, hypertension, diabetes, other cancer, active
disease and hypogammaglobulinemia, but only age 70 years main-
tained independent influence in the multivariate analysis (HR 3.29,
95% CI 1.865.83, p <0.001). Active treatment did not significantly
impact OS (figure 1B). Univariate analysis revealed different prog-
nostic factors, apart from age, for patients with DLBCL (N =60) and
FL (N =69). While the presence of active disease had a prognostic
impact on DLBCL (60day OS 56% vs 79%, p =0.038) but not on FL
(60day OS 65% vs 78%, p =0.181) patients, the opposite occurred in
the case of active treatment, which seemed to have a negative in-
fluence only in patients with FL, as shown in figures 1C and 1D.
Conclusions: Our results confirm a high mortality in patients with
lymphoma and COVID19, especially in those 70 years old. In
patients with DLBCL, disease control seems essential to reduce the
risk of mortality in the event of contracting the infection. By contrast,
in patients with FL, delaying the start of treatment until it is not
strictly necessary should be considered, and these patients should be
prioritized to be vaccinated before starting antitumor treatment. This
study provides initial data to develop recommendations for the
management of lymphoma patients during the COVID19 pandemic.
Keywords: Lymphoid Cancers Other, Therapeutics and Clinical
Trials in Lymphoma Other
No conflicts of interests pertinent to the abstract.
286 bis | SEROLOGICAL RESPONSES AFTER SARSCOV2
VACCINATION FIRST DOSE IN PATIENTS WITH LYMPHOID
MALIGNANCY: FIRST INTERIM ANALYSIS OF THE UK PROSECO
STUDY
S. H. Lim,
1,2
N. Campbell,
3
D. JosephPietras,
4
M. Johnson,
5
C.
Mundy,
2
H. Coleman,
2
T. Wynn,
4
B. Maynard,
3
R. Lown,
3
A. Bates,
3
N.
Wetherall,
3
D. Muller,
3
J. Falconer,
3
C. Fox,
6
G. Collins,
7
A. O'Call-
aghan,
8
V. Willimott,
9
M. Ahearne,
10
S. N. Faust,
3
P. W. Johnson,
1,2
D.
Goldblatt,
5
A. J. Davies.
1,2,4
1
Centre for Cancer Immunology, University of Southampton,
Southampton, UK,
2
Cancer Research UK Centre, University of
Southampton, UK,
3
University Hospital Southampton NHS Foundation
Trust, Southampton, UK,
4
NIHR/Cancer Research UK Southampton
FIGURE 1 Overall survival in the whole series (A), and according to active treatment in the whole series (B), in patients with diffuse large
Bcell lymphoma (DLBCL) (C) and in patients with follicular lymphoma(FL) (D)
SUPPLEMENT ABSTRACTS
-
381
Experimental Medicine Cancer Centre, WISH Laboratory, University
Hospital Southampton, UK,
5
Great Ormond Street Institute of Child
Health, University College London, London, UK,
6
Nottingham University
Hospitals NHS Trust, Nottingham, UK,
7
Oxford University Hospitals NHS
Foundation Trust, Oxford, UK,
8
Portsmouth Hospitals University NHS
Trust, Portsmouth, UK,
9
Norfolk and Norwich University Hospitals NHS
Foundation Trust, Norwich, UK,
10
University Hospitals of Leicester NHS
Trust, Leicester, UK
Introduction: A populationwide SARSCoV2 vaccination pro-
gramme commenced in the UK in December 2020. Two vaccines
have been widely deployed; BNT162b2 (Pfizer) and a ChAdOx1
nCoV19 (Astra Zeneca) both encoding the full length of the spike (S)
protein. The vaccines are administered in two doses 12 weeks apart,
as opposed to 3weekly in other countries. Studies in healthy in-
dividuals indicate that a single dose of the vaccine induces detectable
antiS IgG antibodies in most adults.
Patients with lymphoid malignancies risk more severe COVID19
and are also likely to be poor vaccine responders. PROSECO is a
prospective observational study to evaluate the robustness and
persistence of SARSCoV2 vaccine responses, and identify baseline
clinical parameters correlated to vaccine responses.
Methods: Patients with a confirmed lymphoma diagnosis undergo
blood sampling prior to vaccination, 4 weeks after the first dose, and
24 weeks, 6 and 12 months after the second dose. IgG to SARSCoV
2 Spike, Receptor Binding Domain (RBD) and nucleocapsid protein
are tested using a qualified electrochemiluminescent assay (Meso-
Scale Discovery
®
) calibrated to the WHO International reference
serum (NIBSC 20/136) and compared to responses in healthy vol-
unteers. Tcell reactivity against spike protein will be assessed by
ELISpot.
Results: This first interim analysis reports the serological response of
44 participants with lymphoma (6 Hodgkin lymphoma, 12 diffuse
large B cell lymphoma, 16 follicular lymphoma, 2 mantle cell lym-
phoma, 2 chronic lymphocytic leukaemia, 2 marginal zone lymphoma,
4 peripheral Tcell lymphoma), and data from 49 healthy volunteers
analysed on the same platform, 4 weeks after their first dose of
vaccination. Postvaccination antiS IgG levels were significantly
lower in patients with lymphoma (geometric mean 3.4 U/ml)
compared to healthy participants (geometric mean 331.3 U/ml
(Pfizer) and 66.5 U/ml (Astra Zeneca)). Among patients vaccinated
during systemic antilymphoma therapy, only 2/26 had antiS IgG
>10 Units/ml, compared to 11/18 patients who have had no treat-
ment, or who completed therapy >6 months before the first vacci-
nation dose. In the posttreatment group, patients with curable
disease (n =5) had antiS IgG levels comparable to healthy partici-
pants. In contrast, the serological response in incurable indolent
lymphomas, 4/8 cases exhibiting poor responses despite never being
treated or completed treatment >3 years previously.
Conclusions: This initial analysis indicates that patients with lym-
phoma receiving treatment have a reduced serological response (14
fold vs untreated) to the first dose of SARSCoV2 vaccination and
suggests a rationale for prompt administration of the second dose.
Patients with indolent lymphoma showed persistently poor serolog-
ical responses irrespective of treatment and might benefit from
further vaccine boosters.
Keywords: Lymphoid Cancers Other
Conflicts of interests pertinent to the abstract
S. N. Faust:
Fees to his institution for participation in advisory boards related to
vaccine, or grants for contract commercial clinical trials, were paid to
SNF's institution (with no personal payment of any kind) from
AstraZeneca/Medimmune, Sanofi, Pfizer, Seqirus, Merck, GSK, J&J,
Merck and Valneva, outside the submitted work.
A. J. Davies:
Research support and honoraria from Astra Zeneca.
G. Collins:
Honoraria from Astra Zeneca and Pfizer, and research support from
Pfizer.
M. Ahearne:
Research support from Pfizer.
287 |EFFICACY AND SAFETY OF DARATUMUMAB FOR THE
TREATMENT OF MULTIPLE MYELOMA: A SERIES OF COCHRANE
REVIEWS
C. Hirsch
1
, V. Piechotta
1
, P. Langer
1
, C. Scheid
2
, L. John
3
, N. Skoetz
4
1
Cochrane Haematology, Department I of Internal Medicine, Center for
Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of
Medicine and University Hospital, University of Cologne, Cologne, Germany,
2
Department I of Internal Medicine, Center for Integrated Oncology Aachen
Bonn Cologne Duesseldorf, Stem Cell Transplantation Program, Faculty of
Medicine and University Hospital, University of Cologne, Cologne, Germany,
3
Department of Hematology, Oncology and Rheumatology, University
Hospital Heidelberg, Heidelberg, Germany,
4
Cochrane Cancer, Department
I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne
382
-
SUPPLEMENT ABSTRACTS
Duesseldorf, Faculty of Medicine and University Hospital, University of
Cologne, Cologne, Germany
Introduction: Daratumumab has approved indications for the treat-
ment of patients with newly diagnosed multiple myeloma (NDMM)
both eligible and ineligible for transplant and treatment of relapsed
or refractory multiple myeloma (RRMM). The aim was to evaluate the
efficacy and safety of daratumumab for transplantineligible NDMM
patients (PICO 1), transplant eligible NDMM patients (PICO 2) and
for RRMM patients (PICO 3).
Methods: For each PICO we conduct one Cochrane review according
to the standard methodology as outlined in the Cochrane Handbook
for Systematic Reviews of Interventions, and assess the certainty in
the evidence using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) approach. Our prioritised
outcomes were overall survival, adverse events (CTCAE grade 3)
and quality of life.
Results: Transplantineligible NDMM: We identified two RCTs
(MAIA, ALCYONE) reporting on 1443 patients. Treatment with
daratumumab probably increases overall survival (HR 0.67, 95% CI
0.5 to 0.85, I
2
39%, moderatecertainty evidence), results in a slight
increase of adverse events (grade 3) (RR 1.05, 95% CI 1.0 to 1.11, I
2
26%, highcertainty evidence), more people probably gain at least 10
points of global health status after start of treatment when compared
to people receiving no daratumumab (RR 1.13, 95% CI 1.13 to 1.23, I
2
0%, moderatecertainty evidence).
Transplantineligible NDMM: We identified two RCTs (CASSIO-
PEIA, GRIFFIN) reporting on 1292 patients. GRIFFIN included 207
patients, but did not report any of our crucial outcomes. Treat-
ment with daratumumab may increase overall survival (HR 0.52,
95% CI 0.33 to 0.82, lowcertainty evidence), results in a
slight increase of adverse events (grade 3) (RR 1.06, 95% CI 1.0
to 1.13, highcertainty evidence), more people may gain at least
10 points of global health status after start of treatment compared
to people receiving no daratumumab (RR 1.07, 95% CI 0.91 to
1.24, lowcertainty evidence) at 9.0 months after start of
treatment.
RRMM: We identified four RCTs (CANDOR, CASTOR, LEPUS,
POLLUX) reporting on 1717 patients. Treatment with dar-
atumumab probably increases overall survival (HR 0.62, 95% CI
0.49 to 0.79, I
2
7%, moderatecertainty evidence). We were able to
include safety data from two trials (CASTOR, POLLUX) for 1044
patients. Treatment with daratumumab probably results in a slight
increase of adverse events (grade 3) (RR 1.17, 95% CI 1.04 to
1.31, I
2
64%, moderatecertainty evidence) and more people may
gain at least 10 points of global health status after start of treat-
ment compared to people receiving no daratumumab (RR 1.07, 95%
CI 1.07 to 1.22, I
2
0%, lowcertainty evidence) at 9 months after
start of treatment.
Conclusions: Treatment with daratumumab is likely to retrieve gain
in survival, increases the risk of adverse events (grade 3) and may
contribute to a clinically important improvement of quality of life.
EA previously submitted to EHA 2021.
Keywords: Multiple Myeloma
No conflicts of interests pertinent to the abstract.
SUPPLEMENT ABSTRACTS
-
383
DOI: 10.1002/hon.2881
SUPPLEMENT ABSTRACTS
PUBLICATION
LYMPHOMA BIOLOGY
288 |CCL2CCR2 AXIS SIGNALING PROMOTES DIFFUSE
LARGE BCELL LYMPHOMA CELL SURVIVAL AND INVASION
L. YanLi
1
1
Anhui Medical University the First Affiliated Hospital of Anhui Medical
University, Pathology, Hefei, Anhui, China
Objective: Diffuse large B cell lymphoma (DLBCL) incidence rates
have increased year by year, a part of them have poor clinical
outcomes, but the underlying mechanism involved is still unclear.
Chemokines have been thought to play an important role in
occurrence and development of tumors, but they are poorly studied
in DLBCL. CCChemokine Ligand 2 (CCL2), the most representative
of the CC chemokine family members, through binding to its high
affinity receptor, CC chemokine receptor 2 (CCR2), has be regarded
to involve in tumor growth, angiogenesis, epithelial mesenchymal
transition, metastasis and immune escape etc. in recent years, but
the role and mechanism in DLBCL has not been reported yet. Our
preliminary study showed high expression of CCL2 or CCR2 was
correlated with clinicopathological characteristics, and an adverse
prognostic factor for overall survival (OS) and progressionfree
survival (PFS) of DLBCL patients. The purpose of this study is to
investigate the role of CCL2CCR2 axis signaling in DLBCL by in
vitro experiment.
Methods: CCL2 and CCR2 expression were analyzed in human
DLBCL cell lines and normal B lymphocytes by Western blot (WB)
and qPCR. CCL2 and CCR2 genes were silenced by lentivirus infec-
tion. The proliferation, migration, apoptosis and signaling pathway
were detected by CCK8, transwell, flow cytometry (FC) and WB,
respectively.
Results: CCL2 and CCR2 were expressed in all human DLBCL cell
lines (SUDHL2, SUDHL4, SUDHL6, OCILy8 and OCILy10).
Blockade of CCL2CCR2 axis signaling with lentivirus infection, CCL2
neutralizing antibody or CCR2 antagonist inhibited tumor cell pro-
liferation, migration and antiapoptosis ability. The CCL2CCR2 axis
involved in the proliferation and migration of DLBCL cells by acti-
vating PI3K/Akt signaling pathway, and induced apoptosis through
activation of P38MARK signaling pathway.
Conclusions: Our study demonstrates that CCL2/CCR2 axis signaling
plays an important role in the development of DLBCL by stimulating
cell proliferation, migration and antiapoptosis. The inhibition of
CCL2 or CCR2 may, therefore, be a potential target for anticancer
therapy in DLBCL.
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
289 |ACETYLCOA ACETYLTRANSFERASE 1 ACTS AS A
TUMOR SUPPRESSOR IN MALIGNANT TUMORS
X. Hu
1
, Y. Zhang
2
, Y. Han
1
, X. Zhang
1
, Z. Tian
1
, X. Wang
2
1
Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong
University, Department of Hematology, Jinan, China,
2
Shandong
Provincial Hospital Affiliated to Shandong University, Shandong First
Medical University, Department of Hematology, Jinan, China
Background: AcetylCoA acetyltransferase 1 (ACAT1) is an enzyme
to catalyze reversible formation of acetoacetylCoA. Yet, the roles of
ACAT1 in malignant progression have been incompletely understood
so far. Hence, the aim of this study was to investigate the function
and significance of ACAT1 in tumors.
Methods: In the present study, clinically annotated tumor patients
from multiple cohorts were enrolled with informed consents. Gene
expression analysis is completed through the TIMER2 web and
GEPIA2 web, based on the combination of the HPA, GTEx, and
FANTOM5 datasets. The data of protein expression is acquired from
the CPTAC dataset. The statistical significance of survival prognosis
is analyzed by logrank test through the GEPIA2 web. Genetic
alteration analysis is accomplished by cBioPortal web.
Results: Aberrantly alleviated expression of ACAT1 was detected in
multiple tumors at mRNA level compared with normal cells
(Figure 1A). After including the normal tissue of the GTEx dataset as
controls, we further evaluated the expression difference of ACAT1.
ACAT1 expression levels were significantly downregulated (tumor
versus normal) in tumor cases (Figure 1B). Similarly, the outcome of
decreased protein level of ACAT1 (tumor versus normal) could be
obtained (Figure 1C). We divided the cancer cases into high
expression and lowexpression groups according to the expression
levels of ACAT1 and investigated the correlation of ACAT1
expression with the prognosis of patients with different tumors.
KaplanMeier curves showed stratified ACAT1
low
group were
observed with significantly shorter overall survival (OS) and disease
free survival (DFS) versus the ACAT1
high
group in mutiple malignant
© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
384
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Hematological Oncology. 2021;39(S2):384484. wileyonlinelibrary.com/journal/hon
tumors (Figure 1D and 1E). In hematological cancer, ACAT1
high
group showed a better overall survival than ACAT1
low
group in
multiple myeloma and Bcell lymphoma (Figure 1F). Then, We
observed the genetic alteration status of ACAT1 in different tumor
samples of the TCGA cohorts. As shown in Figure 1G, the highest
alteration frequency of ACAT1 (>7%) appears for patients with
uterine tumors. The “deletion” type of copy number alteration (CNA)
was the primary type in melanoma and cervical carcinoma cases,
which show an alteration frequency of 23% (Figure 1G). The
types, sites, and case number of the ACAT1 genetic alteration
SUPPLEMENT ABSTRACTS
-
385
are further presented in Figure 1H. We found that missense muta-
tion of ACAT1 was the main type of genetic alteration (N=48)
(Figure 1H). Additionally, we explored the potential association be-
tween genetic alteration of ACAT1 and the clinical survival prognosis
of cases with different types of cancer. The data of Figure 1I indi-
cated a better overall survival in cases without altered ACAT1
compared with cases with ACAT1 alteration in variety of
malignancies.
Conclusion: Taken together, the present study was the first pan
cancer analysis on the role of ACAT1 in tumors. ACAT1 was down
regulated and conferred independent prognostic significance, high-
lighting the effectiveness and potential of ACAT1 as a potential
target for future therapeutic strategies.
EA previously submitted to EHA 2021.
The research was funded by: This study was funded by National Nat-
ural Science Foundation (No.82000195, No.82070203, No.81770210,
No.81473486 and No.81270598); Key Research and Development
Program of Shandong Province (No.2018CXGC1213); Technology
Development Projects of Shandong Province (No.2017GSF18189);
Translational Research Grant of NCRCH (No.2021WWB02,
No.2020ZKMB01); Shandong Provincial Natural Science Foundation
(No.ZR2020QH094); Taishan Scholars Program of Shandong Province;
Shandong Provincial Engineering Research Center of Lymphoma; Ac-
ademic Promotion Programme of Shandong First Medical University
(No. 2019QL018; No.2020RC007); Technology Development Project
of Jinan City (No.200027182); Shandong Provincial Hospital Youth
Talent Plan; Shandong Provincial Hospital Research Incubation Fund.
Keywords: Bioinformatics, Computational and Systems Biology,
Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
290 |CONCURRENT COMPOSITE LYMPHOMAS
COLLECTIVELY BEARING THREE DIAGNOSTIC ENTITIES OF
SHARED CLONAL ORIGIN
W. Alduaij
1
, M. Al Moosawi
2
, H. Leitch
3
, J. Craig
4
1
BC Cancer, Lymphoid Cancer Research, Vancouver, Canada,
2
University of British Columbia, Hematological Pathology, Department of
Pathology and Laboratory Medicine, Vancouver, Canada,
3
University of
British Columbia, Hematology, Vancouver, Canada,
4
BC Cancer,
Department of Pathology and Laboratory Medicine, Vancouver, Canada
Introduction: Composite lymphoma (CL) is defined as the coexistence
of two distinct lymphoma subtypes in a single biopsy, whereas
discordant lymphoma (DL) is their occurrence at different anatomical
sites. Although CL/DL with two distinct lymphomas are a well
described phenomenon, the diagnosis of three lymphomas simulta-
neously is a much rarer occurrence, with only a few cases reported in
the literature. We report a unique case involving two composite
lymphomas collectively bearing three distinct diagnostic entities:
diffuse large Bcell lymphoma (DLBCL), classic Hodgkin lymphoma
(cHL) and follicular lymphoma (FL).
Case report: A 48yearold man presented with cervical lymph-
adenopathy and a tongue mass. Cervical lymph node biopsy
revealed a composite tumour consisting of cHL and DLBCL with a
germinal centre Bcell (GCB) phenotype by Hans algorithm. In
contrast, the tongue mass biopsy revealed a composite tumour of a
morphologically and immunophenotypically similar DLBCL, with FL
grade 3B as evidenced by uniform atypical centroblastic cells
exhibiting a nodular growth pattern suggestive of neoplastic follicle
formation confirmed by intact CD21positive follicular dendritic
cell meshwork. Images highlighting the distinct morphological and
immunohistochemical features of all tumour components will
be presented. The DLBCL components showed no evidence of
MYC rearrangement using breakapart fluorescence in situ hybrid-
ization probes. In situ hybridization for Epstein Barr virus RNA was
positive in the Hodgkin cells in the cHL component but negative in
the other tumours. Although multiplex polymerase chain reaction
analysis using BIOMED2 primers failed to identify clonal rear-
rangements in IGH, the same clonal IGK rearrangement was
detected in all four tumour components, consistent with a shared
Bcell clonal origin. The VkKde/intronKde reaction identified a
single prominent peak at 377 base pair (bp) length amplified by the
Vk2f/Vk4/Vk5Kde primer set, consistent with a clonal Bcell
population (VkKde 3, Fig. 1AC). The same peak was identified
in all four tumour components, including the nodal cHL, albeit at a
lower amplitude in keeping with the lower tumour cell content
of cHL (Fig. 1D). The patient sustained a complete remission
following rituximab, cyclophosphamide, doxorubicin, vincristine and
prednisone.
Conclusion: This case represents an exceedingly rare example of
simultaneous composite lymphomas and the concurrent diagnosis of
three histologically distinct lymphoma subtypes. It also highlights the
limitations of IGHbased clonality testing in germinal centre Bcell
derived lymphomas and underscores the importance of adequate
tissue sampling to facilitate definitive diagnosis. Given the paucity of
data on optimal therapy for these heterogeneous lymphomas, the
treatment approach should be individualized, considering all disease
components.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Pathology and
Classification of Lymphomas
No conflicts of interests pertinent to the abstract.
386
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SUPPLEMENT ABSTRACTS
291 |COMPREHENSIVE TRANSCRIPTOME ANALYSIS
IDENTIFIES DISTINCT COMPETING ENDOGENOUS RNA
NETWORK IN CHRONIC LYMPHOCYTIC LEUKEMIA
Y. Zhang
1
, X. Zhang
1
, Y. Han
1
, Z. Tian
1
, X. Hu
1
, X. Wang
1
1
Shandong Provincial Hospital Affiliated to Shandong First Medical
University, Department of Hematology, Jinan, China
Introduction: Increasing studies have identified that noncoding
RNAs play critical roles in the initiation and progression of tumors
via participating in competitive endogenous RNA (ceRNA) networks.
However, the roles and functions of the ceRNA network in chronic
lymphocytic leukemia (CLL) remain poorly understood. This study
aims to explore the molecular mechanism of CLL and provide po-
tential prognostic markers and therapeutic targets through the in-
tegrated analysis of the ceRNA network in CLL.
Methods: The expression profile of RNAS of CLL patients, CLL cell
lines (MEC1 and EHEB) and healthy group were obtained by the
illumina sequencing. R software was used for functional enrichment
analysis. The data in the genome microarray map GSE22762 was
used for survival analysis. The lncRNA/circRNAmiRNAmRNA
ceRNA networks were visualized by Cytoscape 3.7.2. Four DEmRNAs
and the circRNA hsa_circ_0007675/hsamiR1853p/TCF7L1 axis
were verified by Quantitative realtime PCR.
FIGURE 1
SUPPLEMENT ABSTRACTS
-
387
Results: In the present study, 57 differentially expressed(DE)
mRNAs, 1391 DElncRNAs, 335 DEmiRNAs and 10013 DEcircRNAs
were identified comparing CLL patients with healthy donors.
Meanwhile, 482 mRNAs, 6085 lncRNAs, 302 miRNAs and 1847
circRNAs were explored differently expressed between CLL cell
lines and healthy donors. GO and KEGG analysis results showed
that these differentially expressed genes (DEGs) are related to the
occurrence and development of tumors. The survival analyses
showed that 16 DEGs (INIP, IL3RA, CHD1, NLRP12, IL20RB,
B3GALT4, SIT1, ACOT8, AGFGR, PCLAF, C19orf18, SELENOS,
FIGURE 1
388
-
SUPPLEMENT ABSTRACTS
OR7A17, PCDH7, HNRNPC, PHGDH) were significantly differen-
tially expressed.
The ceRNA network were constructed by Cytoscape software. In
total, 11 mRNA nodes, 19 miRNA nodes, 105 lncRNA nodes were
identified as differentially expressed profiles between CLL patients
and control. Meanwhile, a total of 256 DEcircRNAs, 19 DEmiRNAs,
and 11 DEmRNAs were employed to construct the ceRNA network
between CLL patients and control. We verified four DEGs (TCF7L1,
TRIM34, SLC30A10, HOXD4) and the circRNA hsa_circ_0007675/
hsamiR1853p/TCF7L1 axis. Compared with normal people, the
expression of these four genes and hsa_circ_0007675 in patient
specimens were significantly increased whereas the expression of
hsamiR1853p was downregulated (p <0.05).
Conclusion: In this study, we identified the expression profile of
RNAs in CLL patients and CLL cell lines. Functional enrichment
analysis and survival analysis revealed the potential functions of
DEGs. The ceRNA network we established can help to further un-
derstand the pathogenesis of CLL and provide potential prognostic
markers and novel therapeutic targets.
The research was funded by: This study was funded by National Natural
Science Foundation (No.82000195, No.82070203, No.81770210,
No.81473486 and No.81270598); Key Research and Development
Program of Shandong Province (No.2018CXGC1213); Technology
Development Projects of Shandong Province (No.2017GSF18189);
Translational Research Grant of NCRCH (No.2021WWB02,
No.2020ZKMB01); Shandong Provincial Natural Science Foundation
(No.ZR2020QH094); Taishan Scholars Program of Shandong Province;
Shandong Provincial Engineering Research Center of Lymphoma; Ac-
ademic Promotion Programme of Shandong First Medical University
(No. 2019QL018, No.2020RC007); Technology Development Project
of Jinan City (No.200027182); Shandong Provincial Hospital Youth
Talent Plan; Shandong Provincial Hospital Research Incubation Fund.
Keywords: Diagnostic and Prognostic Biomarkers, Chronic
Lymphocytic Leukemia (CLL)
No conflicts of interests pertinent to the abstract.
292 |THE ROLE OF MULTIPARAMETRIC FLOW CYTOMETRY
IN DETECTING AND CHARACTERIZING GAMMADELTA TCELL
ENTITIES IN PERIPHERAL BLOOD. SINGLECENTER CASE SERIES
AND LITERATURE REVIEW
F. Martín Moro
1
, I. Martín Rubio
2
, R. Alonso
2
, C. López
2
, J. Marquet
1
,
F. Herrera
2
, I. Delgado Trillo
2
, P. Herrera
1
, J. A. García Vela
2
1
Hospital Universitario Ramón y Cajal, Hematology Department, Madrid,
Spain,
2
Hospital Universitario de Getafe, Hematology Department,
Madrid, Spain
Introduction:Gammadelta (GD) Tcell lymphoid neoplasms are rare
and frequently aggressive tumours whose detection and character-
ization by flow cytometry (FCM) is challenging in a huge proportion
of cases, specially those with leukemic involvement. Sometimes it is
difficult to distinguish between clonal/malignant and normal/poly-
clonal populations. Our aim is to present a case series of GD Tcell
entities focalizing in FCM findings and review the role of FCM
according to the current literature.
Methods: Four different and illustrative cases of GD Tcell expansion
in peripheral blood (>5% of all lymphocytes) occurred in a single
center were reviewed. FCM methodology: eightcolour instrument
(FACSCanto
TM
II) with previous compensation and calibration,
EuroFlow panels (screening LST and complete diagnosis TCLPD.
ALOT and TALL if necessary), LoQ 0.01%, Infinicyt
TM
Software 2.0.
Normal and clonal/pathological GD Tcells populations were
described. Clonally TCRgamma gene rearrangements detection was
performed by multiplex PCR (BIOMED2). A literature review was
performed to describe the characteristics of the most relevant GD
Tcell entities.
Results: Case 1 was diagnosed with hepatosplenic Tcell lymphoma
(HSTL), case 2 with GD Tcell large granular lymphocytic leukemia
(GD TLGL), case 3 with GD TALL (Tcell acute lymphoblastic leu-
kemia/lymphoma), and case 4 with polyclonal GD Tcell expansion
secondary to infectious mononucleosis caused by EBV. Characteris-
tics for each case including the most relevant immunophenotypic
findings by FCM are summarized in Figure 1. Two other GD Tcell
lymphomas were included in the review although their peripheral
blood involvement is scarcely reported: primary cutaneous GD Tcell
lymphoma (PCGDTCL) and monomorphic epitheliotropic intestinal
Tcell lymphoma (MEITL).
Conclusions: The peripheral blood assessment by FCM is able to
distinguish and characterize leukemic GD Tcell entities if the
methodology is correctly performed. The loss of expression of T
cell markers such as CD5 or CD7 is a common finding in GD T
cell neoplasms. Most cases are CD4 negative with a negative to
positive expression of CD8. Although a cytotoxic pattern is com-
mon except for GD TALL there is variability in markers
expression, i.e. CD57, CD16, and Granzyme B. Analysing the Tcell
subset and the expression of other markers such as CD94, TdT,
and CD103v may also be helpful. It is mandatory to integrate FCM
with clinical, morphological, and genetic findings to diagnose ma-
lignant and reactive GD Tcell entities with peripheral blood
involvement.
Keywords: Diagnostic and Prognostic Biomarkers, Imaging and Early
Detection Other, Lymphoid Cancers Other
No conflicts of interests pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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389
390
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293 |TRACKING THE EVOLUTION OF UNTREATED HIGH
INTERMEDIATE/HIGHRISK DIFFUSE LARGE BCELL LYMPHOMA
BY CIRCULATING TUMOR DNA
S. Zhang
1
, T. Zhang
1
, Z. Song
1
, W. Li
1
, J. Yu
1
, J. Zhao
1
, S. Zhou
1
,
Z. Qian
1
, L. Li
1
, L. Qiu
1
, X. Liu
1
, X. Wang
1
, H. Zhang
1
1
Department of Lymphoma, Tianjin Medical University Cancer Institute
and Hospital, National Clinical Research Center of Cancer, Key Laboratory
of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for
Cancer, the SinoUS Center for Lymphoma and Leukemia Research,
Tianjin, China
Background: Diffuse large Bcell lymphoma (DLBCL) is aggressive and
easy to relapse, and the potential to noninvasively monitor tumor
evolutionary dynamics of DLBCL needs to be further established.
Liquid biopsy has been proved a promising method to access tumor
DNA through blood sample. In the current study the feasibility and
clinical significance of circulating tumor DNA (ctDNA) for DLBCL were
assessed.
Methods: A total of 19 tumor biopsy samples and 38 plasma samples
from 40 de novo highintermediate/highrisk DLBCL patients were
evaluated at baseline. Longitudinal blood samples collected under
chemotherapy were also collected. A targeted sequencing gene panel
including 31 genes that are most frequently mutated in lymphoma was
designed for this study. The gene mutation spectrum of DLBCL was
analyzed via a recently developed methodology termed Circulating
SingleMolecule Amplification and Resequencing Technology
(cSMART).
Results: The median age of the patients was 59 years.Variants were
identified in 32 (84%) patients. The mutation of genes detected with
10% or higher ratios include TP53 (42.1%), KMT2D (28.9%), CARD11
(21.1%), CREBBP (15.8%), B2M (15.8%), TNFAIP3 (15.8%), CD79B
(13.2%), EP300 (13.2%), myc (10.5%), TRAF3(10.5%). Compared with
the tumor tissue, ctDNA profiling showed good concordance (67.1%).
More mutation sites could be detected in ctDNA than those in matched
tumor tissue. ctDNA concentration at baseline was correlated with
tumor burden, LDH and IPI score. In addition, patients with mutated
TP53 and B2M before treatment predicted poor prognosis. Serial
ctDNA analysis showed that the concentration of ctDNA has utility for
realtime assessment of treatment response and increase of ctDNA
level could predict progressive disease or clinical recurrence.
Conclusion: Our results demonstrate that ctDNA analysis is a
promising method for detection of mutation spectrum of DLBCL and
disease surveillance during therapy.
EA previously submitted to regional or national meetings (up to
1000 attendees).
The research was funded by: The research was funded by the
Natural Science Foundation of Tianjin (19JCYBJC26500) and the
Clinical Oncology Research Fund of CSCO (YXD2019162).
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive Bcell
nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
294 |TCELL SUBSET COMPOSITION AND FUNCTIONALITY IN
PATIENTS WITH WALDENSTRÖM'S MACROGLOBULINEMIA
K. Amaador
1
, A. W. J. Martens
2
, R. de Boer
2
, J. M. Rietveld
2
,
E. Eldering
2
, M. J. Kersten
1
, A. P. Kater
1
, J. M. I. Vos
1
, S. H. Tonino
1
1
Amsterdam UMC, University of Amsterdam, Department of Hematology,
Cancer Center Amsterdam, Amsterdam, The Netherlands and Lymphoma
and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, Netherlands,
2
Amsterdam Infection & Immunity Institute, Department of Experimental
Immunology, Amsterdam UMC, Amsterdam, The Netherlands,
Amsterdam, Netherlands
Background: Waldenström's macroglobulinemia (WM) is an incur-
able lowgrade Bcell NonHodgkin lymphoma. WM resembles
chronic lymphocytic leukemia (CLL) with regard to biologic and
clinical characteristics. In CLL, extensive abnormalities in Tcell
subset distribution and function have been described. These alter-
ations may contribute to disappointing responses to Tcell directed
immunotherapies. Novel autologous Tcell directed immunotherapy
may improve the outlook for WM patients. However, studies evalu-
ating Tcell functionality in WM are lacking.
Methods: We systematically evaluated peripheral blood (PB) Tcell
subset composition and function in WM patients. PB samples
were collected from treatmentnaive, relapsed and symptomatic
WM patients, HCs and treatmentnaïve CLL patients. Lymphocyte
phenotyping was performed and differences in functionality
were assessed by determining the potential of Tcells to degranu-
late and produce cytokines. Cytotoxic potential was assessed
via engagement of blinatumomab (CD3 x CD19 bispecific Tcell
engager), that redirects Tcells via CD3 to kill CD19
+
tumor
cells. Correlations between Tcell subset numbers, cytokine
production, cytotoxic capacity and markers of disease activity
were performed for treatmentnaïve and pretreated WM
separately.
Results: This study included 16 treatmentnaïve WM patients, 10
pretreated symptomatic WM patients, 21 agematched HCs and 17
treatmentnaïve CLL patients. In WM patients, following cell types
had counts similar to HCs: Tcells (relative), CD4
+
Tcells (relative),
absolute CD4
+
and CD8
+
Tcells, T
fh
cells, T
reg
cells, and Vδ1/ Vδ2 T
cells (relative). This is in contrast to CLL, in which Tcell numbers
(relative) were decreased, absolute CD4
+
and CD8
+
Tcells were
increased compared to HCs, T
fh
, T
reg
, and Vδ1 Tcell numbers were
increased as expected. CD4
+
/CD8
+
Tcell differentiation was normal
in WM as opposed to CLL in which a known skewing towards ter-
minal differentiation in CD8
+
Tcells was observed. No difference in
Vδ2 Tcell count was observed between all groups (Figure 1). No
significant differences were found in cytokine production and
degranulation between CD4
+
and CD8
+
Tcells from WM patients in
comparison with HCs, in contrast to CLL in which decreased amounts
of TNF‐α and increased expression of CD107a were found. Cytotoxic
potential of WMderived Tcells was intact and similar to HCs, while
CLLderived Tcells have impaired cytotoxic response to
blinatumomab.
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391
Conclusion: These data represent the first systematic evaluation of
the Tcell compartment in WM. The qualitative and quantitative
changes in the immune system seen in CLL are not found in WM; T
cell numbers, distribution and functionality seem mostly preserved
even in pretreated patients. These findings are encouraging for
application of Tcell directed immunotherapy in WM, especially for
relapsed/refractory WM.
Keywords: Immunotherapy, Indolent nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
295 |INFLUENCE OF EPSTEIN BARR VIRUS (EBV) EXPRESSION
ON CD4+T CELLS AT THE MICROENVIRONMENT IN PEDIATRIC
HODGKIN LYMPHOMA
O. Jimenez
1
, M. V. Preciado
1
, E. De Matteo
1
, P. Chabay
1
1
Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas
(IMIPP). CONICETGCBA, Hospital de Niños Ricardo Gutiérrez. División
Patología, Buenos Aires, Argentina
Introduction: A unique feature of Hodgkin lymphoma (HL) is the
presence of CD4+T cells that surround, protect, and promote
survival of tumor cells. It was described that primary EBV infection
elicits EBVspecific CD4+T cells with cytotoxic proteins. Since in
Argentina, a high incidence of EBVassociated lymphoma was
described in pediatric cases, our aim was to evaluate EBV influ-
ence on CD4+T cells at the microenvironment in pediatric
patients.
Methods: 42 pediatric patients with HL were included in this study.
EBV presence was evaluated by EBERs in situ hybridization (ISH) and
LMP1 immunohistochemistry (IHC). CD4, CD8, Foxp3, Tbet, GrB,
IL10, PD1 and CD56 markers were analyzed by IHC. Survival was
evaluated by Kaplan Meier analysis.
Results: EBV expression in HRS tumor cells was observed in 78% of
patients by EBERs ISH and LMP1 IHC. Mean CD4+cell count was
not statistically different between EBV+and EBVpatients (p >0.05,
MW test). However, when functional markers of CD4+cells were
evaluated, exclusively in EBV+cases, CD4+cells positively corre-
lated with GrB+cells (p =0.008, r =0.473, Spearman), whereas
neither Foxp3+nor Tbet+cells showed statistical correlation with
CD4+cells (p >0.05, Spearman). CD4+cells also displayed a sta-
tistical positive correlation with CD56+cells, as marker of NK cells
(p =0.006, r =0.488, Spearman), while, in contrast, in EBVcases a
trend to a negative correlation was demonstrated between CD4+
and CD56+cells (p =0.06, r =0.686, Spearman). Furthermore,
CD56+cells did not show a statistical correlation with GrB+cells
(p >0.05, Spearman). In addition, Tbet+cells correlated with Foxp3+
and GrB+cells (p =0.001, r =0.536; p =0.04, r =0.364, respec-
tively) in EBV+cases whereas Foxp3+cells correlated with GrB+
cells (p =0.013, r =0.444, Spearman). All those correlations were not
observed in EBVcases. None of the markers were associated with
event free survival when median cells count was used as cut off value
(p >0.05, long rank test).
Conclusions: This study reflects that CD4 cells in the context of EBV
associated pediatric HL may be involved in cytotoxic activity as
observed in primary infection, and this activity could be direct, since
NK cells were not correlated with cytotoxic GrB marker. In addition,
this cytotoxic and proinflammatory activity of GrB+and Tbet+cells,
respectively, may be counterbalanced by immunoregulatory Foxp3+
cells.
Keywords: Hodgkin lymphoma
No conflicts of interests pertinent to the abstract.
296 |COSTIMULATORY MOLECULE OX40, TUMOR IMMUNE
MICROENVIRONMENT AND RESPONSE TO
IMMUNOCHEMOTHERAPY IN DIFFUSE LARGE BCELL
LYMPHOMA: AN INTEGRATIVE ANALYSIS WITH MOLECULAR
CHARACTERISTICS
X. Wang
1
, Y. Hong
1
, Y. Li
1
, Q. Guan
1
, S. Zhou
1
, Z. Qian
1
, L. Qiu
1
, L. Li
1
,
X. Liu
1
, K. Fu
1
, H. Zhang
1
1
Department of Lymphoma, Tianjin Medical University Cancer Institute
and Hospital, National Clinical Research Center of Cancer, Key Laboratory
of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for
Cancer, the SinoUS Center for Lymphoma and Leukemia Research,
Tianjin, China
Background: OX40 is a crucial Tcell costimulatory molecule, but its
molecular characteristics remain unclear in diffuse large Bcell lym-
phoma (DLBCL).
Methods: We performed an integrative analysis of gene expression,
somatic mutations and multiplex immunofluorescence to charac-
terize the OX40 molecular features, tumor immune microenviron-
ment (TiME) and clinical outcomes.
Results: We first identified that an abnormally higher gene
expression of OX40 existed in DLBCL than other cancers from
discovery cohort, which was validated in two independent cohorts.
Then, we found that elevated OX40 promoted DLBCL patients to
have superior response to immunochemotherapy via activating T
cell from another discovery cohort and validation cohort. Elevated
OX40 drove the recruitment of abundant infiltrating lymphocytes,
leading a higher stromalimmune score in TiME, and positively
corrected with immunerelated genes, including PD1, CTLA4,
TIGIT, VISTA, ICOS, GITR, 41BB and CD28. Tumor mutational
burden was not a mainly driver of host immune responses mediated
by elevated OX40, but BIRC6, STAT6 and TNFRSF14 mutations. In
another validation cohort, patients with high OX40 expression
exhibited lower Ann Arbor stage (p =0.039) and IPI score
(p =0.047), and were easier to achieve CR/PR, especially in both
high OX40 and OX40L expression, and have longer OS (p =0.008)
and PFS (p =0.010). In infiltrated Tcell subsets analysis, patients
392
-
SUPPLEMENT ABSTRACTS
with a greater number of CD4+/OX40+or CD8+/OX40+Tcells
had a longer OS (p =0.021; p =0.009), while the CD8+/OX40+
Tcells also maintained independent prognostic value for survival
(HR =0.517; CI =0.2760.968; p =0.039).
Conclusions: Overall, our findings provide insights for the application
of targeting OX40, or a combined OX40 agonists and firstline
immunochemotherapy in DLBCL patients.
The research was funded by: The research was funded by
Natural Science Foundation of Tianjin grants (19JCYBJC26500),
Clinical Oncology Research Fund of CSCO grants (YXD2019162,
YRoche201920097).
Keywords: Basic and Translational Science Other, Aggressive Bcell
nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
297 |A WIDE TCELL EXHAUSTION PATTERN IS FREQUENTIN
THE TUMOR MICROENVIRONMENT OF RELAPSED/
REFRACTORY BCELL LYMPHOMA PATIENTS AND COULD BE
CIRCUMVENTED BY PDL1 BLOCKADE
C. Laurent
1
, C. Syrykh
1
, C. Herbaux
2
, E. Gat
3
, P. Gravelle
1
, K. Tarte
4
,
G. Cartron
2
, L. Xerri
5
1
IUCTOncopole Toulouse CRCT INSERM U1037, Pathology, Toulouse,
France,
2
CHU Montepellier UMR CNRS 5235, Hematology, Montpellier,
France,
3
LYSARC CHU Lyon Sud, LYSARC, PierreBénite, France,
4
CHU
Rennes Pontchaillou UMR U1236, Immunology, Cell Therapy and He-
matopoiesis, Rennes, France,
5
Institut PaoliCalmettes, Centre de
Recherche en Cancérologie de Marseille, INSERM U1068, CNRS
UMR7258, Pathology, Marseille, France
Background: Relapsed/refractory (R/R) Bcell nonHodgkin lym-
phomas (BNHL) remain incurable diseases and need novel thera-
peutic approaches. In the LYSA trial GATA (NCT03276468), 58
DLBCL and 58 FL R/R patients were treated by obinutuzumab (OBI)
combined with BCL2 inhibitor venetoclax (VEN) and antiPDL1
atezolizumab (ATE) in order to test the synergy of chemofree
tumortargeted therapies. The goal of the present study was to
evaluate the influence of tumor microenvironment (TME) on the ef-
ficiency of this novel drug combination.
Methods: A centralized pathological review was mandatory for
all enrolled cases. As a result, 67 cases including 35 DLBCL
(16 GC and 19 nonGC subtypes) and 32 FL (grade 12) with suf-
ficient relapse material were selected for evaluating TME compo-
sition and immune checkpoints (ICP) expression using standard and/
or multiplexed IHC analyses. All stainings have been scored manu-
ally, and when possible validated using a computerassisted soft-
ware. Biopsy samples at diagnosis were also analyzed in 60%
of cases. Nonparametric tests were used to test correlations be-
tween TME parameters and clinical responses assessed by Lugano
criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and
VEN.
Results: R/R FL exhibited a higher amount of CD3
+
Tcells, CD4
+
T
cells and CTL than R/R DLBCL (p<0.001, p=0.03 and p<0.001).
By contrast, R/R DLBCL contained more CD163
+
macrophages than
R/R FL (p=0.029). TIM3 expression was higher in R/R DLBLC vs R/R FL
(p=0.036), whereas PD1 expression was higher in R/R FL than R/R
DLCDL (p=0.008). ICP expression and ME composition did not
significantly vary between GC and nonCG DLBCL subtypes. As
compared to the initial diagnosis, expressions of TIM3 in FL and TIGIT
in DLBCL had a tendency to be increased at relapse, but no difference
in terms of immune cell composition was observed. PD1/PDL1
expression was not correlated with clinical response, whereas higher
expression of TIM3 and TIGIT (>15%) was associated with better
response in R/R FL (50% versus 33% of CR) and R/R DLBCL (40%
versus 0% of CR), respectively.
Conclusions: We show herein that TME composition and ICP
expression are distinct between R/R FL and R/R DLBCL and remain
mostly unchanged after Rchemotherapy compared to initial biopsies,
except for higher TIM3 and TIGIT expression levels. This preliminary
study indicates that high expression of TIGIT in R/R DLBCL and TIM3 in
R/R FL patients are correlated with responsiveness following OBI
VENATE therapy. Thus, TIGIT and TIM3 expression could predict
the efficacy of PD1/PDL1 blockade in these settings. Overall, these
data may reflect the triggering of a global Tcell exhaustion program in
R/R BNHLs, which can be at least in part circumvented by antiPDL1
therapy. In future trials, targeting TIM3 and TIGIT might be considered
as a synergistic strategy to enhance the benefit of PD1/PDL1 blockade
in these patients.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
298 |MICROENVIRONMENT IMMUNE CELLS IN BONE
MARROW AND LYMPH NODE MEASURED BY FLOW
CYTOMETRY CAN PREDICT SURVIVAL IN DIFFUSE LARGE B CELL
LYMPHOMA
L. Korin
1
, S. Cranco
1
, M. L. Fuente
1
, P. Ochoa
1
, A. Vitriu
1
, E. Babuin
1
,
F. Diaz Couselo
2
, A. Novoa
3
, P. Tempra
3
, M. B. Venegas
3
, A. Vijnovich
Baron
4
, N. Tartas
1
, M. R. Custidiano
1
, M. C. Foncuberta
1
, J. C.
Sanchez Avalos
1
1
Instituto Alexander Fleming, Hematology, Buenos Aires, Argentina,
2
Instituto Alexander Fleming, Internal Medicine, Buenos Aires, Argentina,
3
Instituto Alexander Fleming, Flow Cytometry, Buenos Aires, Argentina,
4
Cepacit, Pathology, Buenos Aires, Argentina
Introduction: Tumor microenvironment (TME) in diffuse large Bcell
lymphoma (DLBCL) has recently been in the spotlight. The predictive
role of immune cells (IC) in peripheral blood (PB), bone marrow (BM)
and lymph nodes (LN) has been individually assessed, often using
techniques not widely available. However, data regarding the relative
prognostic impact of TME in each compartment evaluated simulta-
neously in DLBCL is still lacking.
SUPPLEMENT ABSTRACTS
-
393
Aims: To determine the prognostic impact on survival of the
MonocyteLymphocyte prognostic score (MLS) in PB and the per-
centage (%) of IC in the BM and LN measured by flow cytometry (FC)
in DLBCL.
Methods: We retrospectively collected information of patients (pts)
with DLBCL and available BM aspiration and LN FC data at diagnosis,
treated at our center between 2012 and 2019. Pts were stratified
according to the MLS (Wilcox et al, leukemia 2011) in two groups:
low (PB monocyte counts <630/ml and lymphocyte counts 1000/
ml) and intermediatehigh. FC analysis was performed with 8color
panels according to Euroflow protocols. % of BM and LN IC by FC
were compared to normal values determined by Matarraz (Cytom-
etry part B 2010) and Battaglia et al (Immunology 2003), and
analyzed in 3 categories: low, normal and high. Survival analysis was
performed with Kaplanmeier (variables compared with logrank) and
Cox regression.
Results: 71 pts were included with a median age of 59 years. 49.3%
had poor RIPI. All pts received immunochemotherapy. Complete
remission rate was 82%. Median overall survival (OS) was 120.5
months (m), with a median follow up time of 34.7 m.
On univariate analysis TME variables from all the compartments
showed prognostic impact on OS. BM IC levels did not statistically
differ in involved vs not involved BM.
Both low LN TL % and high and low BM Mo % remained in-
dependent predictors of survival on multivariate analysis. Moreover,
pts with both of these unfavorable variables had a HR for death of
40.22 (CI 95% 5.16313.04, p <0.001) with a median OS of only
22.19 m.
Variables
Univariate
analysis Multivariate analysis
HR (95%
CI)
P
value
HR
(95% CI) Pvalue
LN T lymphocytes
(TL) low
3.98
(1.31
12.06)
0.014 5.44 (1.48
20.04)
0.011
BM B lymphocytes
low
4.73
(1.62
13.79)
0.004 3.36 (0.99
11,34)
0.0501
BM Monocytes (Mo)
High
10.53
(3.66
30.26)
<0.001 4.66 (1.34
16.25)
0.015
BM Monocytes Low 3.87
(1.28
11.7)
0.016 3.40 (1.05
10.99)
0.04
PB MLS
intermediatehigh
2.59
(1.12
6)
0.02 1.05 (0.4
2.77)
0.91
Conclusion: Abnormal BM Mo % and low LN TL % measured by FC
were associated with inferior OS in our cohort of DLBCL pts. These
two TME variables presented at diagnosis could be easily translated
FIGURE 1 Kaplanmeler estimates of
overall survival stratified by number of adverse
prognosis tumor microenviroment varaibles
present(low lymph node Tlymphocytes and high
low bone marrow monocytes)
394
-
SUPPLEMENT ABSTRACTS
into prognostic biomarkers in DLBCL, identifying a subgroup of pts
with a dismal short term prognosis. In the future, therapies that
target the crosstalk between lymphoma cells and the LN and BM ME
might represent an encouraging strategy to improve outcomes in this
high risk subset of pts.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
299 |TARGETING DLBCLDERIVED EXOSOMES PREVENTS NK
CELL EXHAUSTION AND ELICITS POTENT ANTITUMOR
IMMUNITY
F. Lu
1
, Y. Pang
1
, Y. Zhao
1
, J. Ye
1
, C. Ji
1
1
Qilu Hospital of Shandong University, Department of Hematology, Jinan,
China
SUPPLEMENT ABSTRACTS
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395